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Phase II Copanlisib in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

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: NCT02391116
Recruitment Status : Completed
First Posted : March 18, 2015
Results First Posted : January 8, 2018
Last Update Posted : January 4, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diffuse, Large B-Cell, Lymphoma
Intervention Drug: Copanlisib (Aliqopa, BAY80-6946)
Enrollment 67
Recruitment Details The study was conducted at 32 centers across 10 countries, between 08 May 2015 (first patient first visit) and 18 January 2018 (last patient last visit).
Pre-assignment Details A total of 91 participants were screened, of which 67 were assigned to study treatment and also started the treatment, and 24 were screened but never assigned to treatment. Altogether 27 participants were excluded from the per protocol set, which comprised 40 participants.
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
Hide Arm/Group Description Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Period Title: Treatment
Started 67
Included in Per Protocol Set 40
Completed 53 [1]
Not Completed 14
Reason Not Completed
Withdrawal by Subject             1
Protocol Violation             1
Adverse Event (AE) Without Clinical PD             9
AE with Clinical PD             3
[1]
Reasons for completion in this period included death (2), PD (50) and lack of efficacy (1)
Period Title: Safety Follow-up
Started 56 [1]
Completed 43 [2]
Not Completed 13
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             4
Switching to Other Therapy             4
No Follow Up             1
Deterioration of General Conditions             3
[1]
This period excludes 2 deaths on treatment and 9 participants entering active follow-up
[2]
14 participants were considered completed due to death
Period Title: Active Follow-up
Started 9 [1]
Completed 6 [2]
Not Completed 3
Reason Not Completed
Withdrawal by Subject             1
Switching to Other Therapy             2
[1]
This period incorporates safety follow-up with radiological
[2]
Reasons for completion in this period included death (2) and PD (4)
Period Title: Survival Follow-up
Started 46 [1]
Completed 42 [2]
Not Completed 4
Reason Not Completed
Withdrawal by Subject             3
Switching to Other Therapy             1
[1]
21 participants discontinued from treatment didn't enter due to withdrawal by subject (3) and death
[2]
Reason for completed in this period included death (35) and clinical endpoint reached (7)
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
Hide Arm/Group Description Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Overall Number of Baseline Participants 67
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Full analysis set (FAS) Number Analyzed 67 participants
65.3  (14.5)
Per protocol set (PPS) Number Analyzed 40 participants
69.2  (12.2)
[1]
Measure Analysis Population Description: Full analysis set (FAS) and per protocol set (PPS)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Full analysis set (FAS) Number Analyzed 67 participants
Female
28
  41.8%
Male
39
  58.2%
Per protocol set (PPS) Number Analyzed 40 participants
Female
15
  37.5%
Male
25
  62.5%
[1]
Measure Analysis Population Description: Full analysis set (FAS) and per protocol set (PPS)
CD79b Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Full analysis set (FAS) Number Analyzed 67 participants
CD79b Mutant
9
  13.4%
CD79b Wild-type
45
  67.2%
CD79b Status Missing
13
  19.4%
Per protocol set (PPS) Number Analyzed 40 participants
CD79b Mutant
8
  20.0%
CD79b Wild-type
32
  80.0%
CD79b Status Missing
0
   0.0%
[1]
Measure Analysis Population Description: Full analysis set (FAS) and per protocol set (PPS)
DLBCL / Cell of Origin (COO) Subtype   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Full analysis set (FAS) Number Analyzed 67 participants
Activated B-cell-like (ABC)
19
  28.4%
Germinal center B-cell-like (GCB)
30
  44.8%
Unclassifiable
3
   4.5%
DLBCL/COO Subtype Missing
15
  22.4%
Per protocol set (PPS) Number Analyzed 40 participants
Activated B-cell-like (ABC)
16
  40.0%
Germinal center B-cell-like (GCB)
22
  55.0%
Unclassifiable
2
   5.0%
DLBCL/COO Subtype Missing
0
   0.0%
[1]
Measure Analysis Population Description: Full analysis set (FAS) and per protocol set (PPS)
1.Primary Outcome
Title Objective Response Rate (ORR) in Total Population Based on Investigator Assessment
Hide Description The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
Time Frame From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) and per protocol set (PPS)
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
Hide Arm/Group Description:
Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Overall Number of Participants Analyzed 67
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
Full analysis set (FAS) Number Analyzed 67 participants
19.4
(11.9 to 29.1)
Per protocol set (PPS) Number Analyzed 40 participants
25.0
(14.2 to 38.7)
2.Primary Outcome
Title ORR by CD79b Status Based on Investigator Assessment
Hide Description The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
Time Frame From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) and per protocol set (PPS)
Arm/Group Title CD79b Mutant CD79b Wild-type CD79b Status Missing
Hide Arm/Group Description:
Included all participants with CD79b mutant classified at baseline depending on the biomarker value
Included all participants with CD79b wild-type classified at baseline depending on biomarker value
Included all participants with CD79b status missing at baseline
Overall Number of Participants Analyzed 9 45 13
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
Full analysis set (FAS) Number Analyzed 9 participants 45 participants 13 participants
22.2
(4.1 to 55.0)
20.0
(10.9 to 32.3)
15.4
(2.8 to 41.0)
Per protocol set (PPS) Number Analyzed 8 participants 32 participants 0 participants
25.0
(4.6 to 60.0)
25.0
(13.1 to 40.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CD79b Mutant, CD79b Wild-type
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Exact confidence intervals (CI)
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 2.2
Confidence Interval (2-Sided) 90%
-28.7 to 32.9
Estimation Comments ORR difference in FAS (N=54): ORR in CD79b mutant subgroup minus ORR in CD79b wild-type subgroup
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection CD79b Mutant, CD79b Wild-type
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Exact confidence intervals (CI)
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 90%
-33.5 to 33.5
Estimation Comments ORR difference in PPS (N=40): ORR in CD79b mutant subgroup minus ORR in CD79b wild-type subgroup
3.Primary Outcome
Title ORR by DLBCL/COO Subtype Based on Investigator Assessment
Hide Description The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
Time Frame From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) and per protocol set (PPS)
Arm/Group Title Activated B-cell-like (ABC) Germinal Center B-cell-like (GCB) Unclassifiable DLBCL/COO Subtype Missing
Hide Arm/Group Description:
Included all participants with activated B-cell-like (ABC) DLBCL classified at baseline depending on the biomarker value
Included all participants with germinal center B-cell-like (GCB) DLBCL classified at baseline depending on the biomarker value
Included all participants with unclassifiable DLBCL/COO subtype at baseline
Included all participants with DLBCL/COO subtype missing at baseline
Overall Number of Participants Analyzed 19 30 3 15
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
Full analysis set (FAS) Number Analyzed 19 participants 30 participants 3 participants 15 participants
31.6
(14.7 to 53.0)
13.3
(4.7 to 28.0)
33.3
(1.7 to 86.5)
13.3
(2.4 to 36.3)
Per protocol set (PPS) Number Analyzed 16 participants 22 participants 2 participants 0 participants
37.5
(17.8 to 60.9)
13.6
(3.8 to 31.6)
50.0
(2.5 to 97.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Activated B-cell-like (ABC), Germinal Center B-cell-like (GCB), Unclassifiable
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Exact confidence intervals (CI)
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 16.4
Confidence Interval (2-Sided) 90%
-7.2 to 39.1
Estimation Comments ORR difference in FAS (N=52): ORR in ABC subgroup minus ORR in non-ABC group (i.e. combined GCB subgroup and Unclassifiable subgroup)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Activated B-cell-like (ABC), Germinal Center B-cell-like (GCB), Unclassifiable
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Exact confidence intervals (CI)
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 20.8
Confidence Interval (2-Sided) 90%
-6.8 to 46.2
Estimation Comments ORR difference in PPS (N=40): ORR in ABC subgroup minus ORR in non-ABC group (i.e. combined GCB subgroup and Unclassifiable subgroup)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Activated B-cell-like (ABC), Germinal Center B-cell-like (GCB), Unclassifiable
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Exact confidence intervals (CI)
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value -18.5
Confidence Interval (2-Sided) 90%
-40.1 to 4.6
Estimation Comments ORR difference in FAS (N=52): ORR in GCB subgroup minus ORR in non-GCB subgroup (i.e. combined ABC subgroup and Unclassifiable subgroup)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Activated B-cell-like (ABC), Germinal Center B-cell-like (GCB), Unclassifiable
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Exact confidence intervals (CI)
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value -25.3
Confidence Interval (2-Sided) 90%
-49.1 to 1.1
Estimation Comments ORR difference in PPS (N=40): ORR in GCB subgroup minus ORR in non-GCB subgroup (i.e. combined ABC subgroup and Unclassifiable subgroup)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Activated B-cell-like (ABC), Germinal Center B-cell-like (GCB), Unclassifiable
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Exact confidence intervals (CI)
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 12.9
Confidence Interval (2-Sided) 90%
-42.4 to 63.2
Estimation Comments ORR difference in FAS (N=52): ORR in Unclassifiable subgroup minus ORR in ABC / GCB subgroup (i.e. combined ABC subgroup and GCB subgroup)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Activated B-cell-like (ABC), Germinal Center B-cell-like (GCB), Unclassifiable
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Exact confidence intervals (CI)
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Difference
Estimated Value 26.3
Confidence Interval (2-Sided) 90%
-44.3 to 77.6
Estimation Comments ORR difference in PPS (N=40): ORR in Unclassifiable subgroup minus ORR in ABC / GCB subgroup (i.e. combined ABC subgroup and GCB subgroup)
4.Secondary Outcome
Title Duration of Response (DOR) in Total Population
Hide Description The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. participants with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Responders (i.e. participants with a best response of CR or PR) in full analysis set based on the investigator assessment
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
Hide Arm/Group Description:
Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Overall Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: Days
132
(57 to 345)
5.Secondary Outcome
Title DOR by CD79b Status
Hide Description The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. participants with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Responders (i.e. participants with a best response of CR or PR) in full analysis set based on the investigator assessment
Arm/Group Title CD79b Mutant CD79b Wild-type CD79b Status Missing
Hide Arm/Group Description:
Included all participants with CD79b mutant classified at baseline depending on the biomarker value
Included all participants with CD79b wild-type classified at baseline depending on biomarker value
Included all participants with CD79b status missing at baseline
Overall Number of Participants Analyzed 2 9 2
Median (95% Confidence Interval)
Unit of Measure: Days
516
(417 to 615)
113
(39 to 272)
113
(93 to 132)
6.Secondary Outcome
Title DOR by DLBCL/COO Subtype
Hide Description The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. participants with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Responders (i.e. participants with a best response of CR or PR) in full analysis set based on the investigator assessment
Arm/Group Title Activated B-cell-like (ABC) Germinal Center B-cell-like (GCB) Unclassifiable DLBCL/COO Subtype Missing
Hide Arm/Group Description:
Included all participants with activated B-cell-like (ABC) DLBCL classified at baseline depending on the biomarker value
Included all participants with germinal center B-cell-like (GCB) DLBCL classified at baseline depending on the biomarker value
Included all participants with unclassifiable DLBCL/COO subtype at baseline
Included all participants with DLBCL/COO subtype missing at baseline
Overall Number of Participants Analyzed 6 4 1 2
Median (95% Confidence Interval)
Unit of Measure: Days
193
(39 to 417)
183
(63 to 615)
52 [1] 
(NA to NA)
113
(93 to 132)
[1]
Value cannot be estimated due to censored data.
7.Secondary Outcome
Title Progression-free Survival (PFS) in Total Population
Hide Description The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
Hide Arm/Group Description:
Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Overall Number of Participants Analyzed 67
Median (95% Confidence Interval)
Unit of Measure: Days
54
(50 to 84)
8.Secondary Outcome
Title PFS by CD79b Status
Hide Description The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title CD79b Mutant CD79b Wild-type CD79b Status Missing
Hide Arm/Group Description:
Included all participants with CD79b mutant classified at baseline depending on the biomarker value
Included all participants with CD79b wild-type classified at baseline depending on biomarker value
Included all participants with CD79b status missing at baseline
Overall Number of Participants Analyzed 9 45 13
Median (95% Confidence Interval)
Unit of Measure: Days
73
(43 to 465)
52
(46 to 88)
56
(46 to 138)
9.Secondary Outcome
Title PFS by DLBCL/COO Subtype
Hide Description The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Activated B-cell-like (ABC) Germinal Center B-cell-like (GCB) Unclassifiable DLBCL/COO Subtype Missing
Hide Arm/Group Description:
Included all participants with activated B-cell-like (ABC) DLBCL classified at baseline depending on the biomarker value
Included all participants with germinal center B-cell-like (GCB) DLBCL classified at baseline depending on the biomarker value
Included all participants with unclassifiable DLBCL/COO subtype at baseline
Included all participants with DLBCL/COO subtype missing at baseline
Overall Number of Participants Analyzed 19 30 3 15
Median (95% Confidence Interval)
Unit of Measure: Days
73
(44 to 101)
52
(46 to 116)
84
(26 to 164)
51
(33 to 58)
10.Secondary Outcome
Title Overall Survival (OS) in Total Population
Hide Description The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
Hide Arm/Group Description:
Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Overall Number of Participants Analyzed 67
Median (95% Confidence Interval)
Unit of Measure: Days
224
(104 to 327)
11.Secondary Outcome
Title OS by CD79b Status
Hide Description The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title CD79b Mutant CD79b Wild-type CD79b Status Missing
Hide Arm/Group Description:
Included all participants with CD79b mutant classified at baseline depending on the biomarker value
Included all participants with CD79b wild-type classified at baseline depending on biomarker value
Included all participants with CD79b status missing at baseline
Overall Number of Participants Analyzed 9 45 13
Median (95% Confidence Interval)
Unit of Measure: Days
178 [1] 
(57 to NA)
242
(73 to 385)
224
(56 to 388)
[1]
Value cannot be estimated due to censored data.
12.Secondary Outcome
Title OS by DLBCL/COO Subtype
Hide Description The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Activated B-cell-like (ABC) Germinal Center B-cell-like (GCB) Unclassifiable DLBCL/COO Subtype Missing
Hide Arm/Group Description:
Included all participants with activated B-cell-like (ABC) DLBCL classified at baseline depending on the biomarker value
Included all participants with germinal center B-cell-like (GCB) DLBCL classified at baseline depending on the biomarker value
Included all participants with unclassifiable DLBCL/COO subtype at baseline
Included all participants with DLBCL/COO subtype missing at baseline
Overall Number of Participants Analyzed 19 30 3 15
Median (95% Confidence Interval)
Unit of Measure: Days
210
(63 to 421)
287
(94 to 436)
164
(93 to 273)
160
(46 to 400)
13.Secondary Outcome
Title Duration of Stable Disease (DOSD) in Total Population
Hide Description The duration of stable disease (DOSD) was defined as the time (in days) from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier. The DOSD was only evaluated in participants failing to achieve a best response of CR or PR, but who achieved SD (stable disease), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who failed to achieve CR or PR but achieved SD in full analysis set based on the investigator assessment
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
Hide Arm/Group Description:
Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Overall Number of Participants Analyzed 14
Median (95% Confidence Interval)
Unit of Measure: Days
106
(73 to 138)
14.Secondary Outcome
Title Disease Control Rate (DCR) in Total Population
Hide Description The disease control rate (DCR) was defined as the percentage of participants who had a best response rating of CR, PR, or SD that was achieved during treatment or within 30 days after termination of study drug. The tumor response was based on investigator assessment according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
Hide Arm/Group Description:
Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Overall Number of Participants Analyzed 67
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
40.3
(30.2 to 51.1)
15.Secondary Outcome
Title DCR by CD79b Status
Hide Description The disease control rate (DCR) was defined as the percentage of participants who had a best response rating of CR, PR, or SD that was achieved during treatment or within 30 days after termination of study drug. The tumor response was based on investigator assessment according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
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Full analysis set (FAS)
Arm/Group Title CD79b Mutant CD79b Wild-type CD79b Status Missing
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Included all participants with CD79b mutant classified at baseline depending on the biomarker value
Included all participants with CD79b wild-type classified at baseline depending on biomarker value
Included all participants with CD79b status missing at baseline
Overall Number of Participants Analyzed 9 45 13
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
55.6
(25.1 to 83.1)
40.0
(27.7 to 53.3)
30.8
(11.3 to 57.3)
16.Secondary Outcome
Title DCR by DLBCL/COO Subtype
Hide Description The disease control rate (DCR) was defined as the percentage of participants who had a best response rating of CR, PR, or SD that was achieved during treatment or within 30 days after termination of study drug. The tumor response was based on investigator assessment according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
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Full analysis set (FAS)
Arm/Group Title Activated B-cell-like (ABC) Germinal Center B-cell-like (GCB) Unclassifiable DLBCL/COO Subtype Missing
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Included all participants with activated B-cell-like (ABC) DLBCL classified at baseline depending on the biomarker value
Included all participants with germinal center B-cell-like (GCB) DLBCL classified at baseline depending on the biomarker value
Included all participants with unclassifiable DLBCL/COO subtype at baseline
Included all participants with DLBCL/COO subtype missing at baseline
Overall Number of Participants Analyzed 19 30 3 15
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
52.6
(32.0 to 72.6)
40.0
(25.0 to 56.6)
33.3
(1.7 to 86.5)
26.7
(9.7 to 51.1)
17.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Hide Description A TEAE was defined as any event arising or worsening after the start of study drug administration until 30 days after the last application.
Time Frame From start of test drug to 30 days after the last test drug intake, assessed up to 2 years after the last participant's first treatment or the last participant dies (whichever occurs first), with an average of 15 weeks for individual participant
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Safety analysis set (SAF)
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
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Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Overall Number of Participants Analyzed 67
Measure Type: Number
Unit of Measure: Participants
Any TEAE 65
Any TESAE 44
18.Other Pre-specified Outcome
Title Time to Response (TTR) in Total Population
Hide Description The time to response (TTR) was defined as the time (days) from start of study treatment to the date of first observed response (first measured CR or PR). TTR was defined for responders only (i.e. participants with CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
Time Frame From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
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Responders (i.e. participants with a best response of CR or PR) in full analysis set based on the investigator assessment
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
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Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Overall Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: Days
52
(49 to 56)
19.Other Pre-specified Outcome
Title ORR in Total Population Based on Central Imaging Review
Hide Description The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The overall response assessment for this outcome measure was based on central imaging review.
Time Frame From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
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Full analysis set
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
Hide Arm/Group Description:
Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
Overall Number of Participants Analyzed 67
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
22.4
(14.3 to 32.4)
20.Other Pre-specified Outcome
Title ORR by CD79b Status Based on Central Imaging Review
Hide Description The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The overall response assessment for this outcome measure was based on central imaging review.
Time Frame From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
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Full analysis set (FAS)
Arm/Group Title CD79b Mutant CD79b Wild-type CD79b Status Missing
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Included all participants with CD79b mutant classified at baseline depending on the biomarker value
Included all participants with CD79b wild-type classified at baseline depending on biomarker value
Included all participants with CD79b status missing at baseline
Overall Number of Participants Analyzed 9 45 13
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
44.4
(16.9 to 74.9)
20.0
(10.9 to 32.3)
15.4
(2.8 to 41.0)
21.Other Pre-specified Outcome
Title ORR by DLBCL/COO Subtype Based on Central Imaging Review
Hide Description The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The overall response assessment for this outcome measure was based on central imaging review.
Time Frame From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
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Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Activated B-cell-like (ABC) Germinal Center B-cell-like (GCB) Unclassifiable DLBCL/COO Subtype Missing
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Included all participants with activated B-cell-like (ABC) DLBCL classified at baseline depending on the biomarker value
Included all participants with germinal center B-cell-like (GCB) DLBCL classified at baseline depending on the biomarker value
Included all participants with unclassifiable DLBCL/COO subtype at baseline
Included all participants with DLBCL/COO subtype missing at baseline
Overall Number of Participants Analyzed 19 30 3 15
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
47.4
(27.4 to 68.0)
13.3
(4.7 to 28.0)
0.0
(0.0 to 63.2)
13.3
(2.4 to 36.3)
Time Frame From start of test drug to 30 days after the last test drug intake, assessed up to 2 years after the last participant's first treatment or the last participant dies (whichever occurs first), with an average of 15 weeks for individual participant
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Copanlisib (Aliqopa, BAY80-6946)
Hide Arm/Group Description Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment
All-Cause Mortality
Copanlisib (Aliqopa, BAY80-6946)
Affected / at Risk (%)
Total   53/67 (79.10%)    
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Copanlisib (Aliqopa, BAY80-6946)
Affected / at Risk (%) # Events
Total   44/67 (65.67%)    
Blood and lymphatic system disorders   
Febrile neutropenia * 1  1/67 (1.49%)  1
Lymphadenopathy * 1  1/67 (1.49%)  1
Thrombocytopenia * 1  1/67 (1.49%)  1
Eye disorders   
Diplopia * 1  1/67 (1.49%)  1
Gastrointestinal disorders   
Abdominal pain * 1  3/67 (4.48%)  3
Colitis * 1  1/67 (1.49%)  1
Gastrointestinal haemorrhage * 1  1/67 (1.49%)  1
Nausea * 1  1/67 (1.49%)  1
Vomiting * 1  1/67 (1.49%)  3
General disorders   
Asthenia * 1  1/67 (1.49%)  1
Death * 1  2/67 (2.99%)  2
Fatigue * 1  1/67 (1.49%)  1
Pyrexia * 1  4/67 (5.97%)  4
Sudden death * 1  1/67 (1.49%)  1
General physical health deterioration * 1  9/67 (13.43%)  9
Infections and infestations   
Cystitis * 1  1/67 (1.49%)  1
Herpes zoster * 1  1/67 (1.49%)  1
Lower respiratory tract infection * 1  1/67 (1.49%)  1
Pneumonia pneumococcal * 1  1/67 (1.49%)  1
Thrombophlebitis septic * 1  1/67 (1.49%)  1
Urosepsis * 1  1/67 (1.49%)  1
Escherichia urinary tract infection * 1  1/67 (1.49%)  1
Lung infection * 1  2/67 (2.99%)  3
Respiratory tract infection viral * 1  1/67 (1.49%)  1
Splenic infection fungal * 1  1/67 (1.49%)  1
Hepatic infection fungal * 1  1/67 (1.49%)  1
Pneumocystis jirovecii pneumonia * 1  1/67 (1.49%)  1
Investigations   
Amylase increased * 1  1/67 (1.49%)  1
Blood creatinine increased * 1  1/67 (1.49%)  1
Lipase increased * 1  1/67 (1.49%)  1
Neutrophil count decreased * 1  1/67 (1.49%)  1
Metabolism and nutrition disorders   
Cachexia * 1  1/67 (1.49%)  1
Dehydration * 1  1/67 (1.49%)  1
Hypercalcaemia * 1  1/67 (1.49%)  1
Hyperglycaemia * 1  5/67 (7.46%)  5
Hyponatraemia * 1  1/67 (1.49%)  1
Musculoskeletal and connective tissue disorders   
Back pain * 1  2/67 (2.99%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Inflammatory carcinoma of the breast * 1  1/67 (1.49%)  1
Mycosis fungoides * 1  1/67 (1.49%)  1
Cancer pain * 1  1/67 (1.49%)  1
Nervous system disorders   
Neurological symptom * 1  1/67 (1.49%)  1
Renal and urinary disorders   
Haematuria * 1  1/67 (1.49%)  1
Renal failure * 1  1/67 (1.49%)  1
Urinary retention * 1  1/67 (1.49%)  1
Acute kidney injury * 1  1/67 (1.49%)  1
Respiratory, thoracic and mediastinal disorders   
Acute pulmonary oedema * 1  1/67 (1.49%)  1
Cough * 1  1/67 (1.49%)  1
Dyspnoea * 1  2/67 (2.99%)  2
Pleural effusion * 1  2/67 (2.99%)  2
Pneumonitis * 1  3/67 (4.48%)  3
Skin and subcutaneous tissue disorders   
Stevens-Johnson syndrome * 1  1/67 (1.49%)  1
Vascular disorders   
Hypertension * 1  1/67 (1.49%)  1
Deep vein thrombosis * 1  1/67 (1.49%)  1
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 4%
Copanlisib (Aliqopa, BAY80-6946)
Affected / at Risk (%) # Events
Total   64/67 (95.52%)    
Blood and lymphatic system disorders   
Anaemia * 1  6/67 (8.96%)  6
Neutropenia * 1  9/67 (13.43%)  9
Thrombocytopenia * 1  6/67 (8.96%)  6
Cardiac disorders   
Tachycardia * 1  3/67 (4.48%)  3
Gastrointestinal disorders   
Abdominal pain * 1  5/67 (7.46%)  5
Constipation * 1  11/67 (16.42%)  11
Diarrhoea * 1  25/67 (37.31%)  38
Mouth ulceration * 1  8/67 (11.94%)  8
Nausea * 1  20/67 (29.85%)  23
Stomatitis * 1  5/67 (7.46%)  5
Vomiting * 1  12/67 (17.91%)  13
Paraesthesia oral * 1  3/67 (4.48%)  5
General disorders   
Asthenia * 1  3/67 (4.48%)  3
Chest pain * 1  3/67 (4.48%)  3
Chills * 1  3/67 (4.48%)  3
Fatigue * 1  18/67 (26.87%)  19
Mucosal inflammation * 1  4/67 (5.97%)  4
Oedema peripheral * 1  7/67 (10.45%)  7
Pyrexia * 1  12/67 (17.91%)  12
Infections and infestations   
Upper respiratory tract infection * 1  4/67 (5.97%)  4
Injury, poisoning and procedural complications   
Fall * 1  3/67 (4.48%)  4
Investigations   
Lipase increased * 1  3/67 (4.48%)  3
Lymphocyte count decreased * 1  3/67 (4.48%)  4
Platelet count decreased * 1  5/67 (7.46%)  5
Weight decreased * 1  3/67 (4.48%)  3
White blood cell count decreased * 1  3/67 (4.48%)  3
Metabolism and nutrition disorders   
Hyperglycaemia * 1  21/67 (31.34%)  27
Hypoglycaemia * 1  3/67 (4.48%)  3
Hypokalaemia * 1  8/67 (11.94%)  15
Hyponatraemia * 1  4/67 (5.97%)  6
Hypophosphataemia * 1  3/67 (4.48%)  4
Decreased appetite * 1  10/67 (14.93%)  14
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  4/67 (5.97%)  4
Muscle spasms * 1  6/67 (8.96%)  7
Pain in extremity * 1  3/67 (4.48%)  5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumour pain * 1  4/67 (5.97%)  4
Nervous system disorders   
Dizziness * 1  4/67 (5.97%)  6
Headache * 1  9/67 (13.43%)  9
Paraesthesia * 1  4/67 (5.97%)  6
Psychiatric disorders   
Insomnia * 1  3/67 (4.48%)  3
Respiratory, thoracic and mediastinal disorders   
Cough * 1  12/67 (17.91%)  12
Dyspnoea * 1  5/67 (7.46%)  5
Productive cough * 1  4/67 (5.97%)  4
Oropharyngeal pain * 1  3/67 (4.48%)  3
Skin and subcutaneous tissue disorders   
Dry skin * 1  6/67 (8.96%)  7
Rash * 1  9/67 (13.43%)  10
Vascular disorders   
Haematoma * 1  3/67 (4.48%)  3
Hypertension * 1  27/67 (40.30%)  42
Hypotension * 1  3/67 (4.48%)  3
1
Term from vocabulary, MedDRA (20.1)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
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Name/Title: Therapeutic Area Head
Organization: Bayer
Phone: (+) 1-888-8422937
EMail: clinical-trials-contact@bayer.com
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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02391116    
Other Study ID Numbers: 17119
2014-004848-36 ( EudraCT Number )
First Submitted: February 16, 2015
First Posted: March 18, 2015
Results First Submitted: October 13, 2017
Results First Posted: January 8, 2018
Last Update Posted: January 4, 2019