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Adavosertib Plus Chemotherapy in Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

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: NCT02272790
Recruitment Status : Active, not recruiting
First Posted : October 23, 2014
Results First Posted : November 22, 2019
Last Update Posted : October 8, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Ovarian, Fallopian Tube, Peritoneal Cancer, P53 Mutation
Interventions Drug: Adavosertib
Drug: Paclitaxel
Drug: Carboplatin
Drug: Gemcitabine
Drug: PLD
Enrollment 95
Recruitment Details This multi-center study was conducted at 20 sites: 18 in the USA, 1 in Canada, and 1 in The Netherlands. Ninety-five (95) patients were enrolled; 94 patients received treatment. The first patient started treatment on 2 Feb 2015; the final patients were still receiving treatment and were censored at the time of database lock on 14 Dec 2018.
Pre-assignment Details One hundred twenty-six (126) patients consented and underwent screening; 94 patients passed screening, whereas 32 patients failed screening tests and were not eligible. The Full Analysis Set consists of 94 patients.
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
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Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Period Title: Overall Study
Started 9 39 23 12 6 6
Completed 9 38 23 12 6 6
Not Completed 0 1 0 0 0 0
Reason Not Completed
Physician Decision             0             1             0             0             0             0
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg Total
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Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Total of all reporting groups
Overall Number of Baseline Participants 9 38 23 12 6 6 94
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
58.6  (9.75) 60.9  (8.16) 62.1  (11.29) 60.3  (6.96) 57.3  (14.58) 61.0  (7.16) 60.7  (9.30)
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
63.0
(46 to 72)
60.0
(45 to 76)
62.0
(34 to 85)
58.5
(52 to 76)
58.5
(40 to 72)
60.5
(54 to 70)
60.0
(34 to 85)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Female
9
 100.0%
38
 100.0%
23
 100.0%
12
 100.0%
6
 100.0%
6
 100.0%
94
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Hispanic or Latino
1
  11.1%
6
  15.8%
2
   8.7%
2
  16.7%
0
   0.0%
1
  16.7%
12
  12.8%
Not Hispanic or Latino
8
  88.9%
31
  81.6%
21
  91.3%
10
  83.3%
5
  83.3%
5
  83.3%
80
  85.1%
Unknown or Not Reported
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
2
   2.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 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%
Asian
0
   0.0%
5
  13.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5
   5.3%
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%
Black or African American
2
  22.2%
4
  10.5%
2
   8.7%
0
   0.0%
0
   0.0%
0
   0.0%
8
   8.5%
White
7
  77.8%
24
  63.2%
20
  87.0%
10
  83.3%
6
 100.0%
6
 100.0%
73
  77.7%
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%
Unknown or Not Reported
0
   0.0%
5
  13.2%
1
   4.3%
2
  16.7%
0
   0.0%
0
   0.0%
8
   8.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
7 30 23 12 6 6 84
Canada Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
2 7 0 0 0 0 9
Netherlands Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
0 1 0 0 0 0 1
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
< 65 Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
5
  55.6%
26
  68.4%
14
  60.9%
8
  66.7%
3
  50.0%
3
  50.0%
59
  62.8%
≥ 65 Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
4
  44.4%
12
  31.6%
9
  39.1%
4
  33.3%
3
  50.0%
3
  50.0%
35
  37.2%
ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
PS = 0
5
  55.6%
19
  50.0%
13
  56.5%
4
  33.3%
1
  16.7%
3
  50.0%
45
  47.9%
PS = 1
4
  44.4%
19
  50.0%
10
  43.5%
8
  66.7%
5
  83.3%
3
  50.0%
49
  52.1%
PS = 2
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
PS = 3
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
PS = 4
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: ECOG Performance Status: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory, able to carry out light or sedentary work; 2 = Ambulatory and capable of all self care but unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled, cannot carry on any self care. Totally confined to bed or chair; 5 = Dead.
Time from 1st positive biopsy for disease to consent for this study (mean)  
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
52.0  (11.83) 70.9  (46.42) 62.3  (24.68) 86.1  (55.67) 61.4  (23.88) 65.8  (20.82) 68.0  (38.93)
Time from 1st positive biopsy for disease to consent for this study (median)  
Median (Full Range)
Unit of measure:  Days
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
49.9
(35.9 to 77.1)
54.9
(31.4 to 250.4)
54.1
(30.0 to 113.6)
74.9
(25.1 to 241.0)
62.9
(30.6 to 87.4)
71.1
(41.1 to 90.0)
54.9
(25.1 to 250.4)
Local or Regional Recurrence  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Yes
5
  55.6%
26
  68.4%
17
  73.9%
9
  75.0%
4
  66.7%
6
 100.0%
67
  71.3%
No
4
  44.4%
12
  31.6%
6
  26.1%
3
  25.0%
2
  33.3%
0
   0.0%
27
  28.7%
Time from local/regional recurrence to consent for this study (mean)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 5 participants 26 participants 17 participants 9 participants 4 participants 6 participants 67 participants
12.2  (14.98) 34.3  (51.20) 20.6  (20.23) 47.0  (57.13) 39.3  (27.78) 5.2  (3.61) 28.6  (41.11)
[1]
Measure Description: Sixty-seven (67) patients has a local or regional recurrence.
[2]
Measure Analysis Population Description: Sixty-seven (67) patients has a local or regional recurrence.
Time from local/regional recurrence to consent for this study (median)   [1] [2] 
Median (Full Range)
Unit of measure:  Weeks
Number Analyzed 5 participants 26 participants 17 participants 9 participants 4 participants 6 participants 67 participants
6.1
(3.0 to 38.9)
18.6
(0.6 to 200.4)
16.6
(1.6 to 70.6)
15.4
(0.9 to 177.9)
37.7
(7.6 to 74.3)
5.6
(0.4 to 10.0)
13.0
(0.4 to 200.4)
[1]
Measure Description: Sixty-seven (67) patients has a local or regional recurrence.
[2]
Measure Analysis Population Description: Sixty-seven (67) patients has a local or regional recurrence.
Distant Metastases  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Yes
3
  33.3%
29
  76.3%
11
  47.8%
12
 100.0%
5
  83.3%
5
  83.3%
65
  69.1%
No
6
  66.7%
9
  23.7%
12
  52.2%
0
   0.0%
1
  16.7%
1
  16.7%
29
  30.9%
Histology  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Serous Epithelial Carcinoma
9
 100.0%
33
  86.8%
21
  91.3%
12
 100.0%
4
  66.7%
6
 100.0%
85
  90.4%
Endometrioid Carcinoma
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
Clear Cell Epithelial Carcinoma
0
   0.0%
2
   5.3%
1
   4.3%
0
   0.0%
1
  16.7%
0
   0.0%
4
   4.3%
Transitional Cell/Brenner Carcinoma
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Squamous Cell Epithelial Carcinoma
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Undifferentiated Epithelial Carcinoma
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Mucinous Epithelial Carcinoma
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
1
   1.1%
Mixed Epithelial Carcinoma
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
Missing
0
   0.0%
1
   2.6%
1
   4.3%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.1%
Histological Grade  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
G1 - Well Differentiated
1
  11.1%
1
   2.6%
0
   0.0%
2
  16.7%
0
   0.0%
0
   0.0%
4
   4.3%
G2 - Moderately Differentiated
0
   0.0%
1
   2.6%
1
   4.3%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.1%
G3 - Poorly Differentiated
5
  55.6%
28
  73.7%
15
  65.2%
9
  75.0%
5
  83.3%
3
  50.0%
65
  69.1%
G4 - Undifferentiated
0
   0.0%
3
   7.9%
2
   8.7%
0
   0.0%
1
  16.7%
1
  16.7%
7
   7.4%
GX - Grade cannot be assessed or Not Applicable
2
  22.2%
3
   7.9%
3
  13.0%
1
   8.3%
0
   0.0%
2
  33.3%
11
  11.7%
Missing
1
  11.1%
2
   5.3%
2
   8.7%
0
   0.0%
0
   0.0%
0
   0.0%
5
   5.3%
Stage at Initial Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
IC
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
IIC
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
1
   1.1%
III
0
   0.0%
1
   2.6%
1
   4.3%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.1%
IIIA
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
2
   2.1%
IIIB
0
   0.0%
2
   5.3%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
3
   3.2%
IIIC
6
  66.7%
14
  36.8%
14
  60.9%
4
  33.3%
1
  16.7%
5
  83.3%
44
  46.8%
IV
3
  33.3%
18
  47.4%
8
  34.8%
8
  66.7%
2
  33.3%
1
  16.7%
40
  42.6%
Missing
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
Metastatic Disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Yes
7
  77.8%
37
  97.4%
19
  82.6%
12
 100.0%
5
  83.3%
6
 100.0%
86
  91.5%
No
2
  22.2%
1
   2.6%
4
  17.4%
0
   0.0%
1
  16.7%
0
   0.0%
8
   8.5%
Sites of Metastatic Disease  
Measure Type: Number
Unit of measure:  Participants
Bone Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
2 1 0 0 0 0 3
Breast Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
0 0 0 2 0 0 2
Distant Lymph Nodes Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
1 14 10 8 3 1 37
Liver Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
6 13 4 3 2 3 31
Local or Regional Lymph Nodes Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
4 20 12 7 1 1 45
Lung Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
1 10 3 2 1 2 19
Other Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
4 31 8 9 5 2 59
Skin or Subcutaneous Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
0 1 0 0 0 0 1
Prior Systemic Therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Yes
9
 100.0%
38
 100.0%
23
 100.0%
12
 100.0%
6
 100.0%
6
 100.0%
94
 100.0%
No
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Time from end of most recent prior systemic therapy to consent for this trial (mean)  
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
11.0  (9.54) 14.4  (15.45) 10.5  (7.81) 15.4  (15.12) 12.9  (11.36) 13.4  (12.08) 13.1  (12.75)
Time from end of most recent prior systemic therapy to consent for this trial (median)  
Median (Full Range)
Unit of measure:  Weeks
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
5.4
(2 to 25)
6.9
(1 to 82)
6.9
(0 to 27)
9.4
(2 to 53)
10.5
(2 to 32)
12.2
(1 to 36)
7.6
(0 to 82)
Number of prior treatment regimens  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
3
  33.3%
12
  31.6%
8
  34.8%
4
  33.3%
3
  50.0%
2
  33.3%
32
  34.0%
2
6
  66.7%
16
  42.1%
9
  39.1%
5
  41.7%
3
  50.0%
4
  66.7%
43
  45.7%
3
0
   0.0%
10
  26.3%
6
  26.1%
2
  16.7%
0
   0.0%
0
   0.0%
18
  19.1%
>3
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
1
   1.1%
Disease setting for most recent prior regimen  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Neoadjuvant
0
   0.0%
4
  10.5%
2
   8.7%
2
  16.7%
0
   0.0%
1
  16.7%
9
   9.6%
Adjuvant
4
  44.4%
15
  39.5%
13
  56.5%
4
  33.3%
4
  66.7%
1
  16.7%
41
  43.6%
Metastatic
5
  55.6%
19
  50.0%
8
  34.8%
6
  50.0%
2
  33.3%
4
  66.7%
44
  46.8%
Disease setting for most recent prior regimen  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Adj/Neoadj in Localized disease (Stage I or II)
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
2
   2.1%
Adjuvant in advanced disease (Stage III or IV)
4
  44.4%
14
  36.8%
13
  56.5%
4
  33.3%
3
  50.0%
1
  16.7%
39
  41.5%
Neoadjuvant in advanced disease (Stage III or IV)
0
   0.0%
3
   7.9%
2
   8.7%
2
  16.7%
0
   0.0%
1
  16.7%
8
   8.5%
Metastatic
5
  55.6%
19
  50.0%
8
  34.8%
6
  50.0%
2
  33.3%
4
  66.7%
44
  46.8%
Missing
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
Best overall response to most recent prior regimen  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Complete Response (CR)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
2
  33.3%
3
   3.2%
Partial Response (PR)
0
   0.0%
2
   5.3%
1
   4.3%
1
   8.3%
0
   0.0%
1
  16.7%
5
   5.3%
Non-CR/Non-PD
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
Stable Disease (SD)
2
  22.2%
4
  10.5%
1
   4.3%
2
  16.7%
1
  16.7%
0
   0.0%
10
  10.6%
Progressive Disease (PD)
2
  22.2%
9
  23.7%
5
  21.7%
4
  33.3%
1
  16.7%
2
  33.3%
23
  24.5%
Not Evaluable
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
Not Applicable
5
  55.6%
21
  55.3%
16
  69.6%
5
  41.7%
3
  50.0%
1
  16.7%
51
  54.3%
Reason most recent prior regimen ended  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Completed planned treatment
4
  44.4%
14
  36.8%
10
  43.5%
5
  41.7%
3
  50.0%
2
  33.3%
38
  40.4%
Progressive Disease
5
  55.6%
19
  50.0%
10
  43.5%
7
  58.3%
2
  33.3%
3
  50.0%
46
  48.9%
Toxicity
0
   0.0%
3
   7.9%
1
   4.3%
0
   0.0%
1
  16.7%
1
  16.7%
6
   6.4%
Other
0
   0.0%
2
   5.3%
2
   8.7%
0
   0.0%
0
   0.0%
0
   0.0%
4
   4.3%
Prior Surgery  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Yes
8
  88.9%
35
  92.1%
22
  95.7%
11
  91.7%
6
 100.0%
6
 100.0%
88
  93.6%
No
1
  11.1%
3
   7.9%
1
   4.3%
1
   8.3%
0
   0.0%
0
   0.0%
6
   6.4%
Prior Radiotherapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
Yes
0
   0.0%
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
No
9
 100.0%
37
  97.4%
23
 100.0%
12
 100.0%
6
 100.0%
6
 100.0%
93
  98.9%
Weight (mean)  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
73.5  (21.56) 73.2  (15.89) 75.7  (19.25) 70.6  (9.45) 70.2  (14.11) 65.7  (8.61) 72.8  (16.12)
Weight (median)  
Median (Full Range)
Unit of measure:  Kilograms
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
69.6
(47.6 to 124.1)
69.6
(47.4 to 117.6)
71.5
(44.8 to 114.0)
67.7
(56.9 to 85.1)
68.2
(56.2 to 95.1)
67.8
(51.1 to 74.4)
69.7
(44.8 to 124.1)
Systolic Blood Pressure (mean)  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
130.0  (15.23) 125.2  (13.37) 127.7  (10.65) 122.3  (6.40) 125.2  (17.22) 127.5  (9.35) 126.1  (12.16)
Systolic Blood Pressure (median)  
Median (Full Range)
Unit of measure:  mmHg
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
130.0
(109.0 to 153.0)
126.5
(100.0 to 159.0)
128.0
(110.0 to 153.0)
121.0
(115.0 to 137.0)
120.0
(112.0 to 159.0)
126.5
(113.0 to 142.0)
126.0
(100.0 to 159.0)
Diastolic Blood Pressure (mean)  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
76.2  (10.96) 76.7  (7.74) 74.8  (8.03) 74.4  (8.26) 73.0  (6.66) 78.7  (6.02) 75.8  (7.99)
Diastolic Blood Pressure (median)  
Median (Full Range)
Unit of measure:  mmHg
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
78.0
(62.0 to 90.0)
78.0
(59.0 to 93.0)
75.0
(61.0 to 95.0)
73.5
(62.0 to 87.0)
74.0
(63.0 to 83.0)
77.5
(73.0 to 89.0)
76.0
(59.0 to 95.0)
Body Surface Area (mean)  
Mean (Standard Deviation)
Unit of measure:  M²
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
1.8  (0.25) 1.8  (0.19) 1.8  (0.22) 1.8  (0.13) 1.8  (0.18) 1.7  (0.10) 1.8  (0.19)
Body Surface Area (median)  
Median (Full Range)
Unit of measure:  M²
Number Analyzed 9 participants 38 participants 23 participants 12 participants 6 participants 6 participants 94 participants
1.8
(1.5 to 2.3)
1.8
(1.4 to 2.3)
1.8
(1.4 to 2.3)
1.7
(1.6 to 2.0)
1.7
(1.6 to 2.1)
1.7
(1.5 to 1.8)
1.7
(1.4 to 2.3)
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria.
Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
1 11 7 8 2 1
2.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description The Disease Control Rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria.
Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
3 27 19 12 3 5
3.Secondary Outcome
Title Duration of Response (DoR)
Hide Description Duration of Response (DoR) is defined as the time from first documented tumour response until the date of documented progression or death from any cause.
Time Frame Throughout the duration of the study, approximately 19 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Duration of Response (DoR) was calculated for all responders (N = 30)
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 1 11 7 8 2 1
Median (95% Confidence Interval)
Unit of Measure: Months
4.4 [1] 
(0 to NA)
12.0 [1] 
(3.7 to NA)
NA [1] 
(NA to NA)
10.4 [1] 
(5.8 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
non calculable
4.Secondary Outcome
Title Progression Free Survival (Median, 80% CI)
Hide Description

Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.

Progression-free survival was derived based on scan/assessment dates, not visit dates.

Time Frame Throughout the Study, Approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Median (80% Confidence Interval)
Unit of Measure: Months
1.7
(1.6 to 5.5)
5.5
(3.8 to 7.1)
4.2
(3.9 to 5.6)
12.0
(8.6 to 13.1)
2.7 [1] 
(1.7 to NA)
NA [1] 
(NA to NA)
[1]
non calculable
5.Secondary Outcome
Title Progression Free Survival (Median, 95% CI)
Hide Description

Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.

Progression-free survival was derived based on scan/assessment dates, not visit dates.

Time Frame Throughout the Study, Approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Median (95% Confidence Interval)
Unit of Measure: Months
1.7
(0.3 to 5.5)
5.5
(3.7 to 7.4)
4.2
(2.8 to 8.9)
12.0 [1] 
(2.7 to NA)
2.7 [1] 
(0.5 to NA)
NA [1] 
(NA to NA)
[1]
non calculable
6.Secondary Outcome
Title Overall Survival (Median, 80% CI)
Hide Description Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.
Time Frame Throughout the Study, Approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Median (80% Confidence Interval)
Unit of Measure: Months
16.0 [1] 
(6.7 to NA)
NA [1] 
(15.6 to NA)
8.9 [1] 
(8.0 to NA)
19.2
(12.4 to 19.2)
3.8
(2.0 to 6.2)
NA [1] 
(NA to NA)
[1]
non calculable
7.Secondary Outcome
Title Overall Survival (Median, 95% CI)
Hide Description Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.
Time Frame Throughout the Study, Approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Median (95% Confidence Interval)
Unit of Measure: Months
16.0 [1] 
(2.2 to NA)
NA [1] 
(11.6 to NA)
8.9 [1] 
(8.0 to NA)
19.2
(12.4 to 19.2)
6.2 [1] 
(2.0 to NA)
NA [1] 
(NA to NA)
[1]
non calculable
8.Secondary Outcome
Title Gynecologic Cancer Intergroup (GCIG) CA-125 Response
Hide Description The GCIG CA-125 response is defined as the proportion of patients achieving a 50% reduction in CA-125 levels from baseline, if baseline level is ≥2 x the upper limit of normal (ULN) within 2 weeks prior to starting treatment. Response must be confirmed and maintained for at least 28 days.
Time Frame Throughout the study, approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
The CA-125 analysis set was comprised of all dosed patients with pre-treatment serum sample showing CA-125 ≥ 2 x ULN within 2 weeks before starting treatment.
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 8 28 15 11 4 4
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percent
25.0
(4.6 to 60.0)
53.6
(36.6 to 69.9)
26.7
(9.7 to 51.1)
63.6
(35.0 to 86.5)
25.0
(1.3 to 75.1)
25.0
(1.3 to 75.1)
9.Secondary Outcome
Title The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.
Hide Description

The number of patients experiencing at least one treatment-related adverse event (TEAE) by maximum CTCAE grade.

Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal

Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
Number of patients with ≥1 TEAE of max Grade 1 0 2 0 0 0 0
Number of patients with ≥1 TEAE of max Grade 2 1 1 5 0 3 4
Number of patients with ≥1 TEAE of max Grade 3 2 19 10 4 3 0
Number of patients with ≥1 TEAE of max Grade 4 6 15 8 8 0 2
Number of patients with ≥1 TEAE of max Grade 5 0 1 0 0 0 0
10.Secondary Outcome
Title The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade
Hide Description

The number and proportion of patients experiencing at least one treatment-related adverse event (TEAE) related to adavosertib by maximum CTCAE grade

Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal

Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
Number of patients with ≥1 TEAE of max Grade 1 0 3 2 0 0 0
Number of patients with ≥1 TEAE of max Grade 2 1 4 5 0 5 4
Number of patients with ≥1 TEAE of max Grade 3 3 16 7 4 1 0
Number of patients with ≥1 TEAE of max Grade 4 5 14 8 8 0 2
Number of patients with ≥1 TEAE of max Grade 5 0 1 0 0 0 0
11.Secondary Outcome
Title The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade
Hide Description

The number of patients experiencing at least one treatment-related adverse event (TEAE) related to chemotherapy by maximum CTCAE grade.

Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal

Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
Number of patients with ≥1 TEAE of max Grade 1 0 4 0 0 0 0
Number of patients with ≥1 TEAE of max Grade 2 1 5 6 0 5 4
Number of patients with ≥1 TEAE of max Grade 3 3 13 8 4 1 0
Number of patients with ≥1 TEAE of max Grade 4 5 15 8 8 0 2
Number of patients with ≥1 TEAE of max Grade 5 0 1 0 0 0 0
12.Secondary Outcome
Title Serious Adverse Events
Hide Description The number of patients experiencing at least one serious adverse event (SAE).
Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
Pts. with ≥ one serious TEAE related to AZD1775. 0 8 9 7 1 1
Pts. with ≥ one serious TEAE related to Chemo. 0 8 9 7 1 1
13.Secondary Outcome
Title Serious Adverse Events Leading to Death
Hide Description The number of patients experiencing at least one serious adverse event (SAE) leading to death.
Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
No. with STEAE related to AZD1775 leading to death 0 1 0 0 0 0
No. with STEAE related to chemo leading to death 0 1 0 0 0 0
14.Secondary Outcome
Title Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation
Hide Description The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment discontinuation.
Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
0 6 5 1 0 0
15.Secondary Outcome
Title Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction
Hide Description The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to dose reduction.
Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
2 18 5 11 0 0
16.Secondary Outcome
Title Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption
Hide Description The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment interruption.
Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
8 30 10 11 0 1
17.Secondary Outcome
Title Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation
Hide Description The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment discontinuation.
Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
0 6 5 1 0 0
18.Secondary Outcome
Title Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction
Hide Description The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to dose reduction.
Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
6 19 8 11 0 0
19.Secondary Outcome
Title Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption
Hide Description The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment interruption.
Time Frame Throughout the duration of the study (up to 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 9 38 23 12 6 6
Measure Type: Number
Unit of Measure: Participants
8 28 12 9 0 1
20.Secondary Outcome
Title Single Dose Adavosertib Cmax
Hide Description Maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.
Time Frame Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
Arm/Group Title Arm A 800 mg/m² Gemcitabine Arm A 1000 mg/m² Gemcitabine Arm B Arm C
Hide Arm/Group Description:

Adavosertib175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 1000 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Overall Number of Participants Analyzed 3 4 7 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
477.4
(3.776%)
571.1
(29.79%)
533.8
(37.29%)
556.6
(56.39%)
21.Secondary Outcome
Title Multiple Dose Adavosertib Cmax
Hide Description Maximum plasma concentration of adavosertib after a multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.
Time Frame Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
Arm/Group Title Arm D 175 mg Arm D 225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 5 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
4135
(65.8%)
23530
(30.15%)
22.Secondary Outcome
Title Single Dose Adavosertib Tmax
Hide Description The time to reach maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.
Time Frame Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
Arm/Group Title Arm A 800 mg/m² Gemcitabine Arm A 1000 mg/m² Gemcitabine Arm B Arm C
Hide Arm/Group Description:

Adavosertib175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.

Gemcitabine 1000 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.

Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Overall Number of Participants Analyzed 3 4 7 6
Median (Full Range)
Unit of Measure: hours
2.00
(1.90 to 2.08)
2.02
(0.50 to 4.05)
4.08
(1.97 to 8.00)
3.15
(1.75 to 4.07)
23.Secondary Outcome
Title Multiple Dose Adavosertib Tmax
Hide Description The time to reach maximum plasma concentration of adavosertib after multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.
Time Frame Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
Arm/Group Title Arm D 175 mg Arm D 225 mg
Hide Arm/Group Description:

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Overall Number of Participants Analyzed 5 4
Median (Full Range)
Unit of Measure: hours
3.92
(1.67 to 4.00)
2.88
(1.87 to 4.00)
Time Frame Throughout the study, approximately 19 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Hide Arm/Group Description Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.

Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles. Carboplatin AUC 5 IV on Day 1 of 21 day cycles.

Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.

Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles.

All-Cause Mortality
Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/9 (55.56%)      12/38 (31.58%)      9/23 (39.13%)      2/12 (16.67%)      3/6 (50.00%)      0/6 (0.00%)    
Hide Serious Adverse Events
Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/9 (44.44%)      17/38 (44.74%)      12/23 (52.17%)      8/12 (66.67%)      2/6 (33.33%)      1/6 (16.67%)    
Blood and lymphatic system disorders             
Anaemia * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 4/23 (17.39%)  4 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Febrile Neutropenia * 1  0/9 (0.00%)  0 3/38 (7.89%)  5 2/23 (8.70%)  2 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Leukopenia * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 1/23 (4.35%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Neutropenia * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1
Pancytopenia * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Thrombocytopenia * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 3/23 (13.04%)  3 5/12 (41.67%)  6 0/6 (0.00%)  0 0/6 (0.00%)  0
Cardiac disorders             
Atrial Fibrillation * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Gastrointestinal disorders             
Abdominal Pain * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 1/23 (4.35%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Colitis * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Diarrhoea * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 2/23 (8.70%)  2 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Ileus * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Intestinal Obstruction * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Nausea * 1  1/9 (11.11%)  1 1/38 (2.63%)  1 2/23 (8.70%)  3 0/12 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Small Intestinal Obstruction * 1  2/9 (22.22%)  3 3/38 (7.89%)  6 1/23 (4.35%)  2 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Vomiting * 1  1/9 (11.11%)  1 1/38 (2.63%)  1 2/23 (8.70%)  3 1/12 (8.33%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
General disorders             
Fatigue * 1  1/9 (11.11%)  1 0/38 (0.00%)  0 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Pyrexia * 1  1/9 (11.11%)  1 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Anaphylactic Reaction * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 0/23 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Immune system disorders             
Chest Pain * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 1/23 (4.35%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Infections and infestations             
Bacteraemia * 1  0/9 (0.00%)  0 3/38 (7.89%)  4 0/23 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Cellulitis * 1  1/9 (11.11%)  1 1/38 (2.63%)  2 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Kidney Infection * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 0/23 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Liver Abscess * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Neutropenic Sepsis * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Paraspinal Abscess * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Sepsis * 1  1/9 (11.11%)  2 0/38 (0.00%)  0 0/23 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Septic Shock * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Urinary Tract Infection * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Vascular Device Infection * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Injury, poisoning and procedural complications             
Gastrointestinal Stoma Complication * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 1/23 (4.35%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Infusion Related Reaction * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 2/23 (8.70%)  2 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Investigations             
Neutrophil Count Decreased * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 1/23 (4.35%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Platelet Count Decreased * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 2/23 (8.70%)  2 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Metabolism and nutrition disorders             
Type 2 Diabetes Mellitus * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 0/23 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Flank Pain * 1  1/9 (11.11%)  1 0/38 (0.00%)  0 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Nervous system disorders             
Transient Ischaemic Attack * 1  0/9 (0.00%)  0 1/38 (2.63%)  1 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Dyspnoea * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 0/23 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Pulmonary Embolism * 1  0/9 (0.00%)  0 1/38 (2.63%)  2 1/23 (4.35%)  1 2/12 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Wheezing * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 0/23 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Skin and subcutaneous tissue disorders             
Skin Ulcer * 1  0/9 (0.00%)  0 0/38 (0.00%)  0 0/23 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A Arm B Arm C Arm C2 Arm D-175 mg Arm D-225 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/9 (100.00%)      38/38 (100.00%)      23/23 (100.00%)      12/12 (100.00%)      6/6 (100.00%)      6/6 (100.00%)    
Blood and lymphatic system disorders             
Anaemia * 1  3/9 (33.33%)  12 24/38 (63.16%)  82 13/23 (56.52%)  45 9/12 (75.00%)  48 3/6 (50.00%)  4 2/6 (33.33%)  2
Neutropenia * 1  4/9 (44.44%)  14 12/38 (31.58%)  25 5/23 (21.74%)  14 11/12 (91.67%)  51 1/6 (16.67%)  1 2/6 (33.33%)  8
Thrombocytopenia * 1  1/9 (11.11%)  3 9/38 (23.68%)  12 11/23 (47.83%)  33 11/12 (91.67%)  90 0/6 (0.00%)  0 0/6 (0.00%)  0
Gastrointestinal disorders             
Abdominal Distension * 1  2/9 (22.22%)  3 2/38 (5.26%)  2 3/23 (13.04%)  3 0/12 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Abdominal Pain * 1  2/9 (22.22%)  2 8/38 (21.05%)  12 8/23 (34.78%)  9 1/12 (8.33%)  4 1/6 (16.67%)  2 2/6 (33.33%)  3
Constipation * 1  1/9 (11.11%)  1 4/38 (10.53%)  4 5/23 (21.74%)  7 4/12 (33.33%)  4 2/6 (33.33%)  2 0/6 (0.00%)  0
Diarrhoea * 1  3/9 (33.33%)  3 31/38 (81.58%)  67 16/23 (69.57%)  33 6/12 (50.00%)  11 1/6 (16.67%)  1 5/6 (83.33%)  9
Dyspepsia * 1  1/9 (11.11%)  1 3/38 (7.89%)  3 2/23 (8.70%)  2 1/12 (8.33%)  1 0/6 (0.00%)  0 2/6 (33.33%)  2
Gastrointestinal Reflux Disease * 1  0/9 (0.00%)  0 4/38 (10.53%)  4 1/23 (4.35%)  2 0/12 (0.00%)  0 3/6 (50.00%)  3 0/6 (0.00%)  0
Nausea * 1  5/9 (55.56%)  9 23/38 (60.53%)  49 19/23 (82.61%)  38 10/12 (83.33%)  12 4/6 (66.67%)  5 4/6 (66.67%)  7
Stomatitis * 1  0/9 (0.00%)  0 3/38 (7.89%)  3 2/23 (8.70%)  2 1/12 (8.33%)  2 2/6 (33.33%)  4 1/6 (16.67%)  1
Vomiting * 1  4/9 (44.44%)  7 19/38 (50.00%)  41 13/23 (56.52%)  24 4/12 (33.33%)  9 3/6 (50.00%)  3 0/6 (0.00%)  0
General disorders             
Fatigue * 1  3/9 (33.33%)  5 23/38 (60.53%)  33 17/23 (73.91%)  30 8/12 (66.67%)  11 3/6 (50.00%)  6 5/6 (83.33%)  5
Oedema, Peripheral * 1  0/9 (0.00%)  0 10/38 (26.32%)  10 0/23 (0.00%)  0 5/12 (41.67%)  5 0/6 (0.00%)  0 0/6 (0.00%)  0
Pyrexia * 1  4/9 (44.44%)  4 8/38 (21.05%)  11 1/23 (4.35%)  1 0/12 (0.00%)  0 1/6 (16.67%)  3 0/6 (0.00%)  0
Infections and infestations             
Urinary Tract Infection * 1  0/9 (0.00%)  0 6/38 (15.79%)  9 2/23 (8.70%)  3 1/12 (8.33%)  1 1/6 (16.67%)  1 1/6 (16.67%)  2
Investigations             
Alanine Aminotransferase Increased * 1  3/9 (33.33%)  3 2/38 (5.26%)  2 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Aspartate Aminotransferase Increased * 1  1/9 (11.11%)  3 4/38 (10.53%)  11 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Blood Alkaline Phosphatase Increased * 1  0/9 (0.00%)  0 3/38 (7.89%)  5 2/23 (8.70%)  3 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Blood Creatinine Increased * 1  0/9 (0.00%)  0 3/38 (7.89%)  3 1/23 (4.35%)  2 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Neutrophil Count Decreased * 1  4/9 (44.44%)  16 13/38 (34.21%)  64 5/23 (21.74%)  17 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Platelet Count Decreased * 1  2/9 (22.22%)  10 7/38 (18.42%)  12 5/23 (21.74%)  19 0/12 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Weight Decreased * 1  1/9 (11.11%)  1 3/38 (7.89%)  3 2/23 (8.70%)  2 0/12 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
White Blood Cell Count Decreased * 1  2/9 (22.22%)  10 11/38 (28.95%)  64 4/23 (17.39%)  17 0/12 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Metabolism and nutrition disorders             
Decreased Appetite * 1  2/9 (22.22%)  3 7/38 (18.42%)  9 5/23 (21.74%)  5 1/12 (8.33%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Dehydration * 1  0/9 (0.00%)  0 3/38 (7.89%)  3 2/23 (8.70%)  4 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Hyperglycaemia * 1  1/9 (11.11%)  2 6/38 (15.79%)  12 3/23 (13.04%)  3 0/12 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Hypoalbuminaemia * 1  0/9 (0.00%)  0 6/38 (15.79%)  18 0/23 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Hypokalaemia * 1  1/9 (11.11%)  1 4/38 (10.53%)  6 2/23 (8.70%)  8 3/12 (25.00%)  4 1/6 (16.67%)  1 0/6 (0.00%)  0
Hypomagnesaemia * 1  1/9 (11.11%)  1 8/38 (21.05%)  13 6/23 (26.09%)  8 2/12 (16.67%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0
Hyponatraemia * 1  1/9 (11.11%)  7 4/38 (10.53%)  6 1/23 (4.35%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Hypophosphataemia * 1  0/9 (0.00%)  0 3/38 (7.89%)  5 0/23 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  2/9 (22.22%)  2 1/38 (2.63%)  1 2/23 (8.70%)  2 3/12 (25.00%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0
Back Pain * 1  1/9 (11.11%)  1 6/38 (15.79%)  6 4/23 (17.39%)  5 3/12 (25.00%)  3 1/6 (16.67%)  1 0/6 (0.00%)  0
Bone Pain * 1  1/9 (11.11%)  1 1/38 (2.63%)  1 1/23 (4.35%)  2 2/12 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Myalgia * 1  0/9 (0.00%)  0 6/38 (15.79%)  6 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Pain in Extremity * 1  1/9 (11.11%)  1 4/38 (10.53%)  4 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Nervous system disorders             
Dizziness * 1  0/9 (0.00%)  0 2/38 (5.26%)  2 3/23 (13.04%)  5 1/12 (8.33%)  1 0/6 (0.00%)  0 2/6 (33.33%)  3
Dysgeusia * 1  1/9 (11.11%)  1 4/38 (10.53%)  4 3/23 (13.04%)  4 4/12 (33.33%)  4 1/6 (16.67%)  1 0/6 (0.00%)  0
Headache * 1  1/9 (11.11%)  1 8/38 (21.05%)  8 7/23 (30.43%)  9 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Peripheral Sensory Neuropathy * 1  0/9 (0.00%)  0 8/38 (21.05%)  14 0/23 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Psychiatric disorders             
Insomnia * 1  1/9 (11.11%)  1 6/38 (15.79%)  6 2/23 (8.70%)  5 1/12 (8.33%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Cough * 1  0/9 (0.00%)  0 5/38 (13.16%)  5 3/23 (13.04%)  3 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Dyspnoea * 1  1/9 (11.11%)  1 10/38 (26.32%)  12 4/23 (17.39%)  4 4/12 (33.33%)  6 0/6 (0.00%)  0 1/6 (16.67%)  2
Epistaxis * 1  1/9 (11.11%)  1 2/38 (5.26%)  2 2/23 (8.70%)  4 1/12 (8.33%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Nasal Congestion * 1  0/9 (0.00%)  0 5/38 (13.16%)  7 2/23 (8.70%)  2 0/12 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Oropharyngeal Pain * 1  1/9 (11.11%)  1 2/38 (5.26%)  3 1/23 (4.35%)  1 2/12 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Skin and subcutaneous tissue disorders             
Alopecia * 1  0/9 (0.00%)  0 6/38 (15.79%)  6 0/23 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Pruritus * 1  2/9 (22.22%)  4 1/38 (2.63%)  1 3/23 (13.04%)  5 0/12 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Rash