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Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor (Rogaratinib)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01976741
Recruitment Status : Completed
First Posted : November 6, 2013
Results First Posted : April 28, 2020
Last Update Posted : May 6, 2021
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms
Interventions Drug: Rogaratinib (BAY1163877) oral solution
Drug: Rogaratinib (BAY1163877) oral tablet
Drug: Rogaratinib (BAY1163877) 800 mg BID
Enrollment 168
Recruitment Details Study was conducted at 29 centers in 7 countries, between 30 Dec 2013 (first subject first visit) and 27 Nov 2019 (last subject last visit).
Pre-assignment Details A total of 988 participants were screened, of whom 168 participants were assigned into the study and received at least one dose of study medication.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Period Title: Overall Study
Started 4 4 4 3 4 4 23 74 8 40
Completed 3 4 1 2 4 4 19 62 7 36
Not Completed 1 0 3 1 0 0 4 12 1 4
Reason Not Completed
Withdrawal by Subject             1             0             1             1             0             0             1             4             0             0
Adverse Event             0             0             2             0             0             0             3             8             1             4
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC) Total
Hide Arm/Group Description Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. Total of all reporting groups
Overall Number of Baseline Participants 4 4 4 3 4 4 23 74 8 40 168
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 4 participants 4 participants 3 participants 4 participants 4 participants 23 participants 74 participants 8 participants 40 participants 168 participants
52.5  (20.4) 58.5  (12.4) 55.8  (15.3) 56.3  (9.8) 56.8  (12.9) 64.3  (8.4) 63.0  (7.8) 66.4  (8.6) 63.4  (11.1) 62.6  (6.6) 63.6  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 3 participants 4 participants 4 participants 23 participants 74 participants 8 participants 40 participants 168 participants
Female
3
  75.0%
2
  50.0%
2
  50.0%
1
  33.3%
1
  25.0%
0
   0.0%
9
  39.1%
20
  27.0%
0
   0.0%
8
  20.0%
46
  27.4%
Male
1
  25.0%
2
  50.0%
2
  50.0%
2
  66.7%
3
  75.0%
4
 100.0%
14
  60.9%
54
  73.0%
8
 100.0%
32
  80.0%
122
  72.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 3 participants 4 participants 4 participants 23 participants 74 participants 8 participants 40 participants 168 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
0
   0.0%
0
   0.0%
1
   0.6%
Not Hispanic or Latino
4
 100.0%
4
 100.0%
4
 100.0%
3
 100.0%
4
 100.0%
4
 100.0%
23
 100.0%
61
  82.4%
8
 100.0%
34
  85.0%
149
  88.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
12
  16.2%
0
   0.0%
6
  15.0%
18
  10.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 3 participants 4 participants 4 participants 23 participants 74 participants 8 participants 40 participants 168 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
1
  25.0%
1
  33.3%
1
  25.0%
1
  25.0%
8
  34.8%
13
  17.6%
1
  12.5%
11
  27.5%
37
  22.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
4
 100.0%
4
 100.0%
3
  75.0%
2
  66.7%
3
  75.0%
3
  75.0%
15
  65.2%
50
  67.6%
7
  87.5%
22
  55.0%
113
  67.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
11
  14.9%
0
   0.0%
7
  17.5%
18
  10.7%
Eastern Cooperative Oncology Group (ECOG) Performance status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 3 participants 4 participants 4 participants 23 participants 74 participants 8 participants 40 participants 168 participants
ECOG=0
2
  50.0%
1
  25.0%
1
  25.0%
1
  33.3%
2
  50.0%
2
  50.0%
10
  43.5%
20
  27.0%
3
  37.5%
14
  35.0%
56
  33.3%
ECOG=1
2
  50.0%
3
  75.0%
3
  75.0%
2
  66.7%
1
  25.0%
1
  25.0%
12
  52.2%
49
  66.2%
5
  62.5%
22
  55.0%
100
  59.5%
ECOG=2
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  25.0%
1
  25.0%
1
   4.3%
5
   6.8%
0
   0.0%
4
  10.0%
12
   7.1%
[1]
Measure Description: ECOG score: 0=fully active; 1=restricted active; 2=ambulatory and capable of all self-care.
1.Primary Outcome
Title Maximum Tolerated Dose (MTD), Defined as Maximum Dose at Which the Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 is Below 20%
Hide Description The MTD was defined as maximum dose at which the incidence of Dose Limiting Toxicities (DLTs) during Cycle 1 is below 20%. DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug. BID=twice daily.
Time Frame Up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
MTD evaluation set: All participants of the total dose-escalation group who completed Cycle 1 or discontinued during Cycle 1 due to an adverse event or DLT.
Arm/Group Title Rogaratinib Total Dose Escalation
Hide Arm/Group Description:
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: mg BID
800
2.Primary Outcome
Title Number of DLTs During Cycle 1
Hide Description DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug.
Time Frame Up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
MTD evaluation set: All participants of the total dose-escalation group who completed Cycle 1 or discontinued during Cycle 1 due to an adverse event or DLT.
Arm/Group Title Rogaratinib Total Dose Escalation
Hide Arm/Group Description:
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: DLTs
0
3.Primary Outcome
Title Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Hide Description Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid pharmacokinetic (PK) data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Arm/Group Title Rogaratinib 100 mg BID Rogaratinib Expansion Food Effect
Hide Arm/Group Description:
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Overall Number of Participants Analyzed 4 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg/L
2760
(56.5%)
11300
(33.8%)
4.Primary Outcome
Title Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Hide Description Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 4 3 4 4 51 11 19 13 2 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg/L
3640
(16.8%)
4360
(36.4%)
5630
(46.2%)
9480
(16.1%)
9060
(32.3%)
10200
(17.3%)
11000
(34.3%)
11000
(47.6%)
10900
(32.5%)
11000
(48.1%)
13900
(52.6%)
11200
(26.0%)
5.Primary Outcome
Title AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Hide Description Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Arm/Group Title Rogaratinib 100 mg BID Rogaratinib Expansion Food Effect
Hide Arm/Group Description:
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Overall Number of Participants Analyzed 4 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg*h/L
15600
(72.0%)
71000
(42.7%)
6.Primary Outcome
Title AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Hide Description Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 3 3 4 4 51 11 19 13 2 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg*h/L
12100
(16.3%)
15300
(41.4%)
33200
(33.1%)
44000
(68.9%)
54300
(31.3%)
55700
(43.5%)
63900
(45.0%)
74200
(49.7%)
63700
(46.5%)
59700
(56.4%)
101000
(37.4%)
66700
(32.0%)
7.Primary Outcome
Title AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Hide Description Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ [lower limit of quantification] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Arm/Group Title Rogaratinib 100 mg BID Rogaratinib Expansion Food Effect
Hide Arm/Group Description:
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Overall Number of Participants Analyzed 4 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg*h/L
20000
(87.3%)
99300
(52.9%)
8.Primary Outcome
Title AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Hide Description Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ [lower limit of quantification] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 3 3 4 4 49 10 19 11 2 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg*h/L
14200
(24.4%)
20100
(57.7%)
43800
(36.3%)
62000
(114%)
78000
(38.5%)
86600
(41.2%)
103000
(53.5%)
121000
(49.3%)
104000
(73.4%)
108000
(33.8%)
172000
(55.3%)
94900
(39.6%)
9.Primary Outcome
Title AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Hide Description Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Arm/Group Title Rogaratinib 100 mg BID Rogaratinib Expansion Food Effect
Hide Arm/Group Description:
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Overall Number of Participants Analyzed 4 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg*h/L
20200
(87.1%)
102000
(55.2%)
10.Primary Outcome
Title AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Hide Description Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 3 3 4 3 46 10 18 11 2 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg*h/L
14300
(24.5%)
20700
(58.1%)
44300
(37.1%)
64000
(118%)
79800
(39.5%)
95400
(48.7%)
109000
(58.4%)
133000
(53.3%)
109000
(77.5%)
115000
(38.9%)
191000
(69.9%)
99600
(46.5%)
11.Primary Outcome
Title Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Hide Description Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Arm/Group Title Rogaratinib 100 mg BID Rogaratinib Expansion Food Effect
Hide Arm/Group Description:
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Overall Number of Participants Analyzed 4 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: /L
0.0276
(56.5%)
0.0141
(33.8%)
12.Primary Outcome
Title Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Hide Description Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 4 3 4 4 51 11 19 13 2 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: /L
0.0728
(16.8%)
0.0436
(36.4%)
0.0282
(46.2%)
0.0237
(16.1%)
0.0151
(32.3%)
0.0127
(17.3%)
0.0138
(34.3%)
0.0137
(47.6%)
0.0137
(32.5%)
0.0137
(48.1%)
0.0174
(52.6%)
0.0140
(26.0%)
13.Primary Outcome
Title AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Hide Description Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Arm/Group Title Rogaratinib 100 mg BID Rogaratinib Expansion Food Effect
Hide Arm/Group Description:
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Overall Number of Participants Analyzed 4 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h/L
0.156
(72.0%)
0.0888
(42.7%)
14.Primary Outcome
Title AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Hide Description Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 3 3 4 4 51 11 19 13 2 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h/L
0.242
(16.3%)
0.153
(41.4%)
0.166
(33.1%)
0.110
(68.9%)
0.0906
(31.1%)
0.0696
(43.5%)
0.0798
(45.0%)
0.0927
(49.7%)
0.0796
(46.5%)
0.0747
(56.4%)
0.126
(37.4%)
0.0834
(32.0%)
15.Primary Outcome
Title AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Hide Description Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Arm/Group Title Rogaratinib 100 mg BID Rogaratinib Expansion Food Effect
Hide Arm/Group Description:
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Overall Number of Participants Analyzed 4 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h/L
0.200
(87.3%)
0.124
(52.9%)
16.Primary Outcome
Title AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Hide Description Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21- days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 3 3 4 4 49 10 19 11 2 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h/L
0.283
(24.4%)
0.201
(57.7%)
0.219
(36.3%)
0.155
(114%)
0.130
(38.5%)
0.108
(41.2%)
0.129
(53.5%)
0.152
(49.3%)
0.130
(73.4%)
0.135
(33.8%)
0.215
(55.3%)
0.119
(39.6%)
17.Primary Outcome
Title AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Hide Description AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Arm/Group Title Rogaratinib 100 mg BID Rogaratinib Expansion Food Effect
Hide Arm/Group Description:
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Overall Number of Participants Analyzed 4 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h/L
0.202
(87.1%)
0.127
(55.2%)
18.Primary Outcome
Title AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Hide Description AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 3 3 4 3 46 10 18 11 2 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h/L
0.286
(24.5%)
0.207
(58.1%)
0.221
(37.1%)
0.160
(118%)
0.133
(39.5%)
0.119
(48.7%)
0.137
(58.4%)
0.166
(53.3%)
0.136
(77.5%)
0.144
(38.9%)
0.239
(69.9%)
0.124
(46.5%)
19.Primary Outcome
Title Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Hide Description Cmax,md (Cmax after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 4 3 3 3 4 4 70 7 15 27 1 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg/L
3940
(38.5%)
4870
(35.2%)
8320
(68.9%)
9490
(63.1%)
10500
(32.6%)
12400
(33.8%)
12600
(34.6%)
11000
(27.9%)
12300
(31.0%)
13100
(33.6%)
13100
12300
(40.5%)
20.Primary Outcome
Title Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Hide Description Cmax/Dmd (Cmax divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 4 3 3 3 4 4 70 7 15 27 1 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: /L
0.0789
(38.5%)
0.0487
(35.2%)
0.0416
(68.9%)
0.0237
(63.1%)
0.0174
(32.6%)
0.0155
(33.8%)
0.0158
(34.6%)
0.0138
(27.9%)
0.0154
(31.0%)
0.0163
(33.6%)
0.0163
0.0153
(40.5%)
21.Primary Outcome
Title AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Hide Description AUC(0-12)md (AUC(0-12) after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 4 3 3 3 4 4 69 7 15 27 1 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg*h/L
13300
(75.4%)
21500
(98.5%)
41700
(27.9%)
61100
(66.2%)
73500
(33.4%)
90900
(28.8%)
85300
(42.8%)
87100
(28.5%)
81700
(44.5%)
84500
(40.8%)
106000
87100
(49.1%)
22.Primary Outcome
Title AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Hide Description AUC(0-12)/Dmd (AUC(0-12) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 4 3 3 3 4 4 69 7 15 27 1 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h/L
0.266
(75.4%)
0.215
(98.5%)
0.209
(27.9%)
0.153
(66.2%)
0.123
(33.4%)
0.114
(28.8%)
0.107
(42.8%)
0.109
(28.5%)
0.102
(44.5%)
0.106
(40.8%)
0.132
0.109
(49.1%)
23.Primary Outcome
Title AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15
Hide Description AUC(0-tlast)md (AUC(0-tlast) after multiple dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 4 3 3 3 4 4 70 7 15 27 1 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg*h/L
12500
(78.5%)
21500
(99.8%)
39200
(19.1%)
60200
(65.8%)
72500
(33.3%)
89000
(30.9%)
81500
(43.4%)
84100
(31.3%)
75000
(44.3%)
83600
(40.8%)
103000
81300
(50.1%)
24.Primary Outcome
Title AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Hide Description AUC(0-tlast)/Dmd (AUC(0-tlast) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 4 3 3 3 4 4 70 7 15 27 1 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h/L
0.250
(78.5%)
0.215
(99.8%)
0.196
(19.1%)
0.151
(65.8%)
0.121
(33.3%)
0.111
(30.9%)
0.102
(43.4%)
0.105
(31.3%)
0.0937
(44.3%)
0.105
(40.8%)
0.129
0.102
(50.1%)
25.Primary Outcome
Title %AE,ur(0-12) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 12 Hours Post Administration) of BAY1163877
Hide Description %AE,ur(0-12) (amount of drug excreted via urine during the collection interval 0 - 12 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Time Frame On Cycle1, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.
Arm/Group Title Rogaratinib 800 mg BID Pooled
Hide Arm/Group Description:
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
Overall Number of Participants Analyzed 13
Median (Full Range)
Unit of Measure: percentage
0.164
(0.0363 to 0.665)
26.Primary Outcome
Title %AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 24 Hours Post Administration) of BAY1163877
Hide Description %AE,ur(0-24) (amount of drug excreted via urine during the collection interval 0 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Time Frame On Cycle1, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.
Arm/Group Title Rogaratinib 800 mg BID Pooled
Hide Arm/Group Description:
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
Overall Number of Participants Analyzed 13
Median (Full Range)
Unit of Measure: percentage
0.180
(0.0587 to 0.695)
27.Primary Outcome
Title %AE,ur(12-24) (Amount of Drug Excreted Via Urine During the Collection Interval 12 - 24 Hours Post Administration) of BAY1163877
Hide Description %AE,ur(12-24) (amount of drug excreted via urine during the collection interval 12 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Time Frame On Cycle1, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.
Arm/Group Title Rogaratinib 800 mg BID Pooled
Hide Arm/Group Description:
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
Overall Number of Participants Analyzed 13
Median (Full Range)
Unit of Measure: percentage
0.0224
(0.0107 to 0.0596)
28.Secondary Outcome
Title Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type
Hide Description Response as defined by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1: complete response (CR: disappearance of all target lesions), partial response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as the reference the baseline sum of diameters), stable disease (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference, the smallest sum of diameters while in the trial), progressive disease (PD: at least a 20% increase in the sum of diameters of the target lesions, taking as a references the smallest sum on study).
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
Arm/Group Title Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 21 22 70 7 37
Measure Type: Count of Participants
Unit of Measure: Participants
missing
2
   9.5%
1
   4.5%
1
   1.4%
1
  14.3%
2
   5.4%
CR
0
   0.0%
0
   0.0%
1
   1.4%
0
   0.0%
0
   0.0%
PD
9
  42.9%
8
  36.4%
20
  28.6%
3
  42.9%
11
  29.7%
PR
0
   0.0%
1
   4.5%
14
  20.0%
1
  14.3%
2
   5.4%
SD
10
  47.6%
12
  54.5%
34
  48.6%
2
  28.6%
22
  59.5%
29.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was defined as the time (days) from the date of the first dose of study drug to the date of the first observed disease progression (radiological or clinical) or death due to any cause, if death occurred before progression was documented. PFS for participants without tumor progression at the time of analysis was censored at their last date of tumor evaluation.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
Arm/Group Title Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 21 22 70 7 37
Median (95% Confidence Interval)
Unit of Measure: Days
45
(41 to 88)
47
(38 to 231)
105
(80 to 109)
44
(24 to 144)
84
(50 to 100)
30.Secondary Outcome
Title Time to Progression (TTP)
Hide Description TTP was defined as the time from start of study treatment until first observed disease progression (radiological or clinical). Progression is defined using RECIST v1.0, as at least a 20% increase in the sum of diameters of the target lesions, taking as a references the smallest sum on study.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
Arm/Group Title Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 21 22 70 7 37
Median (95% Confidence Interval)
Unit of Measure: Days
45
(41 to 76)
47
(38 to 231)
105
(80 to 109)
68
(35 to 295)
85
(50 to 105)
31.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR (for partial and complete response (PR/CR)) was defined as the time (days) from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). DOR was calculated for responders only, i.e. participants with complete or partial response. Therefore, the dose escalation group is not displayed.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a documented objective response of PR or CR.
Arm/Group Title Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 1 15 1 2
Median (95% Confidence Interval)
Unit of Measure: Days
522 [1] 
(NA to NA)
126
(63 to 464)
105 [1] 
(NA to NA)
225
(65 to 385)
[1]
Not Calculated
32.Secondary Outcome
Title Duration of Treatment (DOT)
Hide Description [Not Specified]
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
Arm/Group Title Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 21 22 70 7 37
Median (95% Confidence Interval)
Unit of Measure: Days
51
(39 to 80)
82
(43 to 126)
106
(86 to 119)
49
(12 to 147)
84
(51 to 119)
33.Secondary Outcome
Title Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1
Hide Description Change in serum FGF23 levels from baseline to C2D1 was reported as ratio to baseline (%).
Time Frame From baseline to C2D1
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with FGF23 data available, and participants from expansion groups were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib Dose Expansion
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in a 21-days Cycle in dose escalation phase.
All participants from MTD expansion cohorts.
Overall Number of Participants Analyzed 2 1 2 2 3 4 48
Mean (Standard Deviation)
Unit of Measure: Ratio to baseline (%)
201.5  (106.3) 149.9 441.9  (346.2) 528.0  (290.4) 402.2  (35.2) 517.7  (261.0) 487.0  (447.7)
34.Secondary Outcome
Title Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study
Hide Description [Not Specified]
Time Frame From baseline up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants received at least one dose of Rogaratinib and have valid data for this outcome measure. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
Arm/Group Title Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 18 17 62 6 33
Mean (Standard Deviation)
Unit of Measure: beats per minute
8.22  (12.47) 6.41  (15.60) 6.40  (14.40) 1.42  (11.65) 6.27  (15.02)
35.Secondary Outcome
Title Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study
Hide Description [Not Specified]
Time Frame From baseline up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants received at least one dose of Rogaratinib and have valid data for this outcome measure. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
Arm/Group Title Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 18 17 62 6 33
Mean (Standard Deviation)
Unit of Measure: mmHg
Systolic Blood Pressure -1.33  (16.44) -4.65  (16.73) -2.56  (19.45) -5.00  (12.37) -1.83  (18.85)
Diastolic Blood Pressure -2.50  (13.50) -4.76  (6.99) -0.63  (12.08) -0.58  (9.23) 0.41  (12.55)
36.Secondary Outcome
Title Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15
Hide Description [Not Specified]
Time Frame From baseline up to Cycle 1, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAF): All participants who received at least one dose of the study medication, and valid data for this outcome measure, and participants from dose escalation groups were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 21 22 19 6 18
Mean (Standard Deviation)
Unit of Measure: msec
0.60  (23.11) 12.86  (24.16) 7.82  (29.39) 2.89  (16.47) 6.41  (21.14)
37.Secondary Outcome
Title Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877
Hide Description In order to evaluate the relative bioavailability of the tablet formulation, tablet Cmax/D, AUC(0-tlast)/D, and AUC/D on Cycle 1, Day -3 were compared to solution Cmax/D, AUC(0-tlast)/D, AUC/D on Cycle 1, Day 1 for all analytes. The logarithms of the PK parameters were analyzed using analysis of variance (ANOVA) including participant and formulation effects. Based on these analyses, point estimates (LS-means) and exploratory 90% confidence intervals for the ratios (tablet/solution) of Cmax/D, AUC(0- tlast)/D, and AUC/D were calculated by re-transformation of the logarithmic data using the intra-individual standard deviation of the ANOVA.
Time Frame On Cycle 1, Day -3 and Cycle 1, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants who received both tablet and solution formulation were included in the analysis.
Arm/Group Title Rogaratinib 100 mg BID
Hide Arm/Group Description:
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Overall Number of Participants Analyzed 4
Geometric Least Squares Mean (90% Confidence Interval)
Unit of Measure: ratio
AUC(0-tlast)/D
0.9945
(0.7698 to 1.2847)
AUC/D
0.9776
(0.7609 to 1.2561)
Cmax/D
0.6335
(0.4343 to 0.9240)
38.Secondary Outcome
Title Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Hide Description Tmax (time to reach maximum drug concentration in plasma) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Median and full range were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day -3 and on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 4 3 4 4 51 11 19 13 2 13
Median (Full Range)
Unit of Measure: hours
Cycle 1, Day -3 Number Analyzed 3 participants 4 participants 4 participants 3 participants 4 participants 4 participants 51 participants 10 participants 19 participants 13 participants 2 participants 13 participants
NA [1] 
(NA to NA)
2.02
(0.983 to 3.03)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
2.99
(1.00 to 6.00)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Cycle 1, Day 1 Number Analyzed 3 participants 4 participants 4 participants 3 participants 4 participants 4 participants 51 participants 11 participants 19 participants 13 participants 2 participants 13 participants
0.633
(0.550 to 0.983)
0.783
(0.533 to 0.983)
1.02
(0.617 to 3.25)
1.02
(1.00 to 1.08)
1.54
(1.08 to 2.07)
2.53
(0.517 to 4.05)
2.00
(0.483 to 4.05)
2.00
(0.517 to 8.00)
2.00
(0.500 to 3.25)
1.00
(0.483 to 2.00)
1.28
(0.517 to 2.05)
2.02
(0.500 to 4.00)
[1]
No data at the time point
39.Secondary Outcome
Title Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Hide Description Tlast (time of last plasma concentration above LLOQ) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Median and full range were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day -3 and on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 4 3 4 4 51 11 19 13 2 13
Median (Full Range)
Unit of Measure: hours
Cycle 1, Day -3 Number Analyzed 3 participants 4 participants 4 participants 3 participants 4 participants 4 participants 51 participants 10 participants 19 participants 13 participants 2 participants 13 participants
NA [1] 
(NA to NA)
48.1
(47.9 to 48.4)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
48.0
(46.6 to 48.3)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Cycle 1, Day 1 Number Analyzed 3 participants 4 participants 4 participants 3 participants 4 participants 4 participants 51 participants 11 participants 19 participants 13 participants 2 participants 13 participants
47.7
(46.4 to 47.8)
47.9
(23.9 to 48.3)
47.9
(6.0 to 48.6)
46.9
(24.1 to 48.0)
48.0
(47.7 to 48.1)
47.9
(47.8 to 49.5)
47.9
(11.6 to 49.5)
47.6
(8.0 to 48.2)
47.9
(45.9 to 48.5)
48.0
(11.6 to 49.5)
48.2
(48.1 to 48.3)
47.8
(12.0 to 48.7)
[1]
No data at the time point
40.Secondary Outcome
Title T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Hide Description T1/2 (half-life associated with the terminal slope) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time Frame pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day -3 and on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 3 4 3 3 4 3 46 10 18 11 2 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
Cycle 1, Day -3
NA [1] 
(NA%)
8.15
(22.3%)
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
8.22
(31.6%)
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
Cycle 1, Day 1
8.34
(24.9%)
8.93
(40.2%)
7.51
(19.2%)
7.93
(54.2%)
8.51
(29.4%)
9.29
(9.86%)
11.7
(44.3%)
12.5
(38.7%)
12.3
(52.1%)
11.5
(42.7%)
14.1
(57.7%)
11.4
(41.0%)
[1]
No data at the time point
41.Secondary Outcome
Title Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Hide Description Tmax,md (time to reach maximum drug concentration in plasma after multiple-dose administration) of BAY1163877. Median and full range were reported.
Time Frame pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 4 3 3 3 4 4 70 7 15 27 1 23
Median (Full Range)
Unit of Measure: hours
0.80
(0.50 to 1.10)
1.08
(0.50 to 1.13)
1.12
(1.05 to 4.02)
2.08
(0.50 to 2.17)
2.10
(2.00 to 3.08)
2.56
(1.05 to 5.53)
2.00
(0.00 to 5.53)
3.17
(1.00 to 4.03)
1.98
(0.500 to 4.00)
1.98
(0.500 to 4.07)
2.07
(2.07 to 2.07)
2.00
(0.000 to 4.00)
42.Secondary Outcome
Title Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Hide Description Tlast,md (time of last plasma concentration above LLOQ after multiple-dose administration) of BAY1163877. Median and full range were reported.
Time Frame pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Arm/Group Title Rogaratinib 50 mg BID Rogaratinib 100 mg BID Rogaratinib 200 mg BID Rogaratinib 400 mg BID Rogaratinib 600 mg BID Rogaratinib 800 mg BID Rogaratinib 800 mg BID Pooled Rogaratinib Expansion Food Effect Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description:
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
Overall Number of Participants Analyzed 4 3 3 3 4 4 70 7 15 27 1 23
Median (Full Range)
Unit of Measure: hours
9.80
(6.08 to 11.8)
11.7
(11.6 to 12.3)
11.6
(8.00 to 12.6)
11.7
(11.5 to 11.7)
11.6
(11.5 to 11.8)
11.7
(11.1 to 12.0)
11.7
(6.00 to 12.4)
11.7
(8.62 to 12.1)
11.5
(7.83 to 12.0)
12.0
(8.40 to 12.4)
11.4
(11.4 to 11.4)
11.7
(6.00 to 12.0)
Time Frame From the first study drug administration up to 30 days after the end of treatment with study drug.
Adverse Event Reporting Description The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
 
Arm/Group Title Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Hide Arm/Group Description Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution. Subjects with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. Subjects with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. Subjects with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. Subjects with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
All-Cause Mortality
Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/23 (13.04%)      6/23 (26.09%)      17/74 (22.97%)      2/8 (25.00%)      12/40 (30.00%)    
Hide Serious Adverse Events
Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/23 (39.13%)      14/23 (60.87%)      44/74 (59.46%)      5/8 (62.50%)      24/40 (60.00%)    
Blood and lymphatic system disorders           
Splenic infarction * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Congenital, familial and genetic disorders           
Tracheo-oesophageal fistula * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Eye disorders           
Retinopathy * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Gastrointestinal disorders           
Abdominal discomfort * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Abdominal pain * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Chronic gastritis * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Constipation * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Diarrhoea * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Dysphagia * 1  1/23 (4.35%)  1 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Ileus * 1  1/23 (4.35%)  2 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Nausea * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Small intestinal obstruction * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Vomiting * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Subileus * 1  1/23 (4.35%)  1 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
General disorders           
Death * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Fatigue * 1  1/23 (4.35%)  1 1/23 (4.35%)  1 2/74 (2.70%)  3 0/8 (0.00%)  0 1/40 (2.50%)  1
Pain * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 1/8 (12.50%)  1 0/40 (0.00%)  0
Pyrexia * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 2/74 (2.70%)  2 0/8 (0.00%)  0 1/40 (2.50%)  1
Sudden death * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
General physical health deterioration * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 5/74 (6.76%)  7 1/8 (12.50%)  2 1/40 (2.50%)  1
Multiple organ dysfunction syndrome * 1  0/23 (0.00%)  0 2/23 (8.70%)  2 2/74 (2.70%)  2 0/8 (0.00%)  0 0/40 (0.00%)  0
Hepatobiliary disorders           
Hepatic function abnormal * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Infections and infestations           
Bronchitis * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 2/40 (5.00%)  2
Cellulitis * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Gastrointestinal infection * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Herpes zoster * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Infection * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 1/8 (12.50%)  1 0/40 (0.00%)  0
Kidney infection * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Oesophageal candidiasis * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Pneumonia * 1  1/23 (4.35%)  1 1/23 (4.35%)  2 2/74 (2.70%)  3 1/8 (12.50%)  1 2/40 (5.00%)  2
Sepsis * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Septic shock * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 2/74 (2.70%)  2 0/8 (0.00%)  0 0/40 (0.00%)  0
Urinary tract infection * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 5/74 (6.76%)  8 0/8 (0.00%)  0 0/40 (0.00%)  0
Urosepsis * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 3/74 (4.05%)  3 0/8 (0.00%)  0 0/40 (0.00%)  0
Arthritis bacterial * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Escherichia bacteraemia * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Respiratory tract infection * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  2 0/8 (0.00%)  0 1/40 (2.50%)  1
Injury, poisoning and procedural complications           
Fall * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Spinal compression fracture * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Tracheal obstruction * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 2/40 (5.00%)  3
Investigations           
Amylase increased * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Blood bilirubin increased * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 1/8 (12.50%)  1 0/40 (0.00%)  0
Blood creatinine increased * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Lipase increased * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  2 0/8 (0.00%)  0 0/40 (0.00%)  0
Metabolism and nutrition disorders           
Dehydration * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Hypercalcaemia * 1  1/23 (4.35%)  5 2/23 (8.70%)  4 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Hyperphosphataemia * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Hypoglycaemia * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Hyponatraemia * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Decreased appetite * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 2/74 (2.70%)  2 0/8 (0.00%)  0 0/40 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Back pain * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Groin pain * 1  0/23 (0.00%)  0 1/23 (4.35%)  3 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Neck mass * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Bladder cancer * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Metastases to lung * 1  1/23 (4.35%)  1 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Pharyngeal cancer * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Tumour pain * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 3/74 (4.05%)  4 0/8 (0.00%)  0 0/40 (0.00%)  0
Tumour haemorrhage * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Malignant neoplasm progression * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  2 0/8 (0.00%)  0 0/40 (0.00%)  0
Cancer pain * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Neoplasm progression * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Squamous cell carcinoma * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 1/8 (12.50%)  1 0/40 (0.00%)  0
Nervous system disorders           
Presyncope * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Seizure * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Somnolence * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Spinal cord oedema * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Dural arteriovenous fistula * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Renal and urinary disorders           
Azotaemia * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Haematuria * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Hydronephrosis * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 2/74 (2.70%)  2 0/8 (0.00%)  0 0/40 (0.00%)  0
Pollakiuria * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Renal pain * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Urinary tract obstruction * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Bladder tamponade * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Acute kidney injury * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 2/74 (2.70%)  2 0/8 (0.00%)  0 2/40 (5.00%)  4
Reproductive system and breast disorders           
Perineal pain * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Dyspnoea * 1  3/23 (13.04%)  4 1/23 (4.35%)  1 1/74 (1.35%)  1 0/8 (0.00%)  0 5/40 (12.50%)  8
Haemoptysis * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 0/74 (0.00%)  0 1/8 (12.50%)  1 2/40 (5.00%)  2
Laryngeal pain * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 1/8 (12.50%)  2 0/40 (0.00%)  0
Pleural effusion * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Pleuritic pain * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 1/8 (12.50%)  2 0/40 (0.00%)  0
Pneumothorax * 1  1/23 (4.35%)  1 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Pulmonary haemorrhage * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Respiratory failure * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 2/40 (5.00%)  3
Tracheal stenosis * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Skin and subcutaneous tissue disorders           
Skin ulcer * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Surgical and medical procedures           
Nephrostomy * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 0/8 (0.00%)  0 0/40 (0.00%)  0
Vascular disorders           
Hypotension * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Peripheral vascular disorder * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Arterial haemorrhage * 1  1/23 (4.35%)  1 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 0/40 (0.00%)  0
Peripheral arterial occlusive disease * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
1
Term from vocabulary, MedDRA (22.1)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rogaratinib Total Dose Escalation Rogaratinib Dose Expansion (All Comers) Rogaratinib Dose Expansion (BC) Rogaratinib Dose Expansion (SCCHN) Rogaratinib Dose Expansion (sqNSCLC)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/23 (95.65%)      23/23 (100.00%)      73/74 (98.65%)      8/8 (100.00%)      40/40 (100.00%)    
Blood and lymphatic system disorders           
Anaemia * 1  2/23 (8.70%)  2 4/23 (17.39%)  11 17/74 (22.97%)  29 3/8 (37.50%)  6 12/40 (30.00%)  19
Lymphopenia * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 2/40 (5.00%)  4
Neutropenia * 1  0/23 (0.00%)  0 2/23 (8.70%)  4 0/74 (0.00%)  0 0/8 (0.00%)  0 1/40 (2.50%)  1
Thrombocytopenia * 1  0/23 (0.00%)  0 2/23 (8.70%)  5 0/74 (0.00%)  0 0/8 (0.00%)  0 2/40 (5.00%)  2
Cardiac disorders           
Sinus tachycardia * 1  1/23 (4.35%)  1 1/23 (4.35%)  1 0/74 (0.00%)  0 0/8 (0.00%)  0 2/40 (5.00%)  2
Ear and labyrinth disorders           
Ear pain * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 1/74 (1.35%)  1 1/8 (12.50%)  2 0/40 (0.00%)  0
Eye disorders           
Dry eye * 1  0/23 (0.00%)  0 2/23 (8.70%)  3 12/74 (16.22%)  13 1/8 (12.50%)  2 3/40 (7.50%)  3
Glaucoma * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 4/74 (5.41%)  4 0/8 (0.00%)  0 1/40 (2.50%)  1
Retinal detachment * 1  0/23 (0.00%)  0 1/23 (4.35%)  1 2/74 (2.70%)  3 0/8 (0.00%)  0 2/40 (5.00%)  2
Retinopathy * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 2/40 (5.00%)  2
Growth of eyelashes * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 3/74 (4.05%)  3 1/8 (12.50%)  1 0/40 (0.00%)  0
Detachment of retinal pigment epithelium * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 2/74 (2.70%)  2 0/8 (0.00%)  0 2/40 (5.00%)  2
Pingueculitis * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 2/40 (5.00%)  2
Gastrointestinal disorders           
Abdominal discomfort * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 2/40 (5.00%)  3
Abdominal distension * 1  0/23 (0.00%)  0 2/23 (8.70%)  2 2/74 (2.70%)  2 0/8 (0.00%)  0 2/40 (5.00%)  2
Abdominal pain * 1  0/23 (0.00%)  0 2/23 (8.70%)  2 11/74 (14.86%)  14 0/8 (0.00%)  0 4/40 (10.00%)  4
Abdominal pain upper * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 4/74 (5.41%)  4 1/8 (12.50%)  1 1/40 (2.50%)  1
Ascites * 1  1/23 (4.35%)  2 0/23 (0.00%)  0 1/74 (1.35%)  2 1/8 (12.50%)  1 0/40 (0.00%)  0
Breath odour * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 1/8 (12.50%)  1 0/40 (0.00%)  0
Constipation * 1  2/23 (8.70%)  3 10/23 (43.48%)  16 25/74 (33.78%)  41 3/8 (37.50%)  4 7/40 (17.50%)  10
Diarrhoea * 1  4/23 (17.39%)  8 13/23 (56.52%)  20 48/74 (64.86%)  106 4/8 (50.00%)  5 23/40 (57.50%)  42
Dry mouth * 1  0/23 (0.00%)  0 2/23 (8.70%)  2 25/74 (33.78%)  42 0/8 (0.00%)  0 9/40 (22.50%)  13
Dyspepsia * 1  1/23 (4.35%)  1 2/23 (8.70%)  3 5/74 (6.76%)  5 1/8 (12.50%)  1 4/40 (10.00%)  5
Dysphagia * 1  0/23 (0.00%)  0 2/23 (8.70%)  2 3/74 (4.05%)  3 3/8 (37.50%)  3 2/40 (5.00%)  2
Enterocolitis * 1  0/23 (0.00%)  0 0/23 (0.00%)  0 0/74 (0.00%)  0 0/8 (0.00%)  0 2/40 (5.00%)