Trial Outcomes & Findings for Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas (NCT NCT01660451)

Last Updated: 2024-07-17

Results Overview

Objective response rate was defined as the proportion of participants with a best response rating of CR, CRu or PR, based on the Report of an International Workshop to Standardize Response Criteria for non-Hodgkins Lymphomas, Cheson, 1999. For CLL patients Hallek criteria (2008) were used and assessed by investigator.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

227 participants

Primary outcome timeframe

Baseline up to the last patient has completed the 16 weeks of treatment

Results posted on

2024-07-17

Participant Flow

Part A-Study enrolled participants from 41 study centers in 10 countries, between 19 NOV 2012 (first participant first visit \[FPFV\]) and 13 AUG 2018 (last participant last visit \[LPLV\]). Part B-Study enrolled participants from 81 study centers in 24 countries, between 04 NOV 2013 (FPFV) and 18 MAY 2023 (LPLV),

Part A: Overall 125 participants were screened, of them 41 were screened but never assigned to treatment. Total 84 were assigned to treatment. Part B: Overall 213 participants were screened, of them 70 were screened but never assigned to treatment. Total 143 were assigned to treatment, of them 1 was suspected as fraudulent and excluded from analysis sets. Therefore 142 participants were evaluable.

Participant milestones

Participant milestones
Measure	Part A: Indolent NHL/CLL Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part B: Indolent NHL Participants with indolent B-cell NHL received copanlisib 60 mg or 0.8 mg/kg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
Overall Study STARTED	33	51	142
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	33	51	142

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Indolent NHL/CLL Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part B: Indolent NHL Participants with indolent B-cell NHL received copanlisib 60 mg or 0.8 mg/kg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
Overall Study Protocol Violation	0	1	1
Overall Study AE not associated with clinical disease progression	13	10	40
Overall Study AE associated with clinical disease progression	1	3	11
Overall Study Sponsor Decision	0	0	1
Overall Study Protocol Deviation	0	0	1
Overall Study Physician Decision	1	2	5
Overall Study Withdrawal by Subject	1	1	20
Overall Study Trial closure.	0	0	1
Overall Study Switching to other therapy	0	1	1
Overall Study Progressive disease - clinical progression	4	10	9
Overall Study Progressive disease - radiological progression	12	23	50
Overall Study Death	1	0	1
Overall Study Other	0	0	1

Baseline Characteristics

Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Indolent NHL/CLL n=33 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL n=51 Participants Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part B: Indolent NHL n=142 Participants Participants with indolent B-cell NHL received copanlisib 60 mg or 0.8 mg/kg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Total n=226 Participants Total of all reporting groups
Age, Customized 18 to 90 years	33 Participants n=93 Participants	51 Participants n=4 Participants	142 Participants n=27 Participants	226 Participants n=483 Participants
Sex: Female, Male Female	18 Participants n=93 Participants	22 Participants n=4 Participants	71 Participants n=27 Participants	111 Participants n=483 Participants
Sex: Female, Male Male	15 Participants n=93 Participants	29 Participants n=4 Participants	71 Participants n=27 Participants	115 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants	10 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=93 Participants	36 Participants n=4 Participants	124 Participants n=27 Participants	181 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=93 Participants	13 Participants n=4 Participants	12 Participants n=27 Participants	35 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	15 Participants n=27 Participants	15 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) White	25 Participants n=93 Participants	40 Participants n=4 Participants	120 Participants n=27 Participants	185 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=93 Participants	11 Participants n=4 Participants	7 Participants n=27 Participants	26 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline up to the last patient has completed the 16 weeks of treatment

Population: Per protocol set included all patients treated with study drug and evaluated for ORR and had no major protocol deviation. (In Part A, for CLL patients, there was no independent assessment. Instead, the investigator assessment had been used.)

Objective response rate was defined as the proportion of participants with a best response rating of complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on the Report of an International Workshop to Standardize Response Criteria for non-Hodgkins Lymphomas, Cheson, 1999, as evaluated by the Independent Response Adjudication Committee (IRAC). For chronic lymphocytic leukemia (CLL) patients Hallek criteria (2008) were used and assessed by investigator.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=32 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL n=48 Participants Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
Objective Response Rate (ORR) Based on Independent Review-Part A	43.75 percentage of participants Interval 28.73 to 59.68	27.08 percentage of participants Interval 16.83 to 39.57

PRIMARY outcome

Timeframe: Baseline up to the last patient has completed the 16 weeks of treatment

Population: FAS included all patients assigned to study treatment.

Objective response rate was defined as the proportion of participants with a best response rating of CR or PR, based on the International Working Group Revised response Criteria for Malignant Lymphoma, Cheson 2007.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=142 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
ORR Based on Independent Review-Part B	59.15 percentage of participants Interval 50.6 to 67.32	—

PRIMARY outcome

Timeframe: Baseline up to the last patient has completed the 16 weeks of treatment

Population: Per protocol set included all patients treated with study drug and evaluated for ORR and had no major protocol deviation. Patients who were not evaluable for ORR and discontinued due to a drug-related toxicity, death / progression by clinical judgment before disease was re-evaluated and included.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=32 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL n=48 Participants Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
ORR Based on Investigator Assessment-Part A	46.88 percentage of participants Interval 31.54 to 62.66	31.25 percentage of participants Interval 20.35 to 43.97

PRIMARY outcome

Timeframe: Baseline up to the last patient has completed the 16 weeks of treatment

Population: FAS included all patients assigned to study treatment.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=142 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
ORR Based on Investigator Assessment-Part B	51.41 percentage of participants Interval 42.88 to 59.87	—

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years

Population: PPS included all patients with study drug administration that were evaluable for objective tumor response and had no major protocol deviation. DOR was only evaluated for patients with at least one tumor response of CR, Cru (only for Part A) or PR.

DOR was defined as the time from the date of the first observed tumor response of CR or PR (whichever was noted earlier) to first subsequent disease progression (either first progressive disease \[PD\], first clinical progression or first AE associated with clinical disease progression) or death caused by disease progression, if this death occurred before progression was documented. All deaths were considered as 'caused by disease progression' except deaths with the reason "other" or "AE not related to disease progression. DOR was evaluated only for patients with at least one tumor response of CR, CRu, or PR. Some patients may have had no report of disease progression nor death caused by disease progression until the date of the LPLV. With regards to DOR, these patients were considered as right censored at the date of their last tumor assessment after first observed tumor response.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=14 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL n=14 Participants Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
Duration of Response (DOR) Based on Independent Review-Part A	322 Days Interval 61.0 to NA: Value cannot be estimated due to censored data	NA Days Interval 61.0 to NA: Value cannot be estimated due to censored data

SECONDARY outcome

Timeframe: Baseline up to approximately 9 years 7 months

Population: FAS included all patients assigned to study treatment. DOR was only evaluated for patients with at least one tumor response of CR, Cru (only for Part A) or PR.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=85 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
DOR Based on Independent Review-Part B	14.9 Months Interval 9.2 to 22.6	—

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=15 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL n=15 Participants Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
DOR Based on Investigator Assessment-Part A	189 Days Interval 56.0 to 574.0	190 Days Interval 112.0 to NA: Value cannot be estimated due to censored data

SECONDARY outcome

Timeframe: Baseline up to approximately 9 years 7 months

Population: FAS included all patients assigned to study treatment. DOR was only evaluated for patients with at least one tumor response of CR, Cru (only for Part A) or PR.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=78 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
DOR Based on Investigator Assessment-Part B	11.5 Months Interval 9.2 to 16.1	—

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years

Population: FAS included all patients assigned to study treatment.

PFS was defined as the time (in days) from the date of the first treatment to the date of first observed PD (radiological or clinical, or first AE associated with clinical PD, whichever was earlier) or death due to any cause (if death occurred before progression was documented).

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=33 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL n=51 Participants Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
Progression Free Survival (PFS) Based on Independent Review-Part A	223 Days Interval 147.0 to 546.0	70 Days Interval 47.0 to 115.0

SECONDARY outcome

Timeframe: Baseline up to approximately 9 years 7 months

Population: FAS included all patients assigned to study treatment.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=142 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
PFS Based on Independent Review-Part B	11.3 Months Interval 8.1 to 17.6	—

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years

Population: FAS included all patients assigned to study treatment.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=33 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL n=51 Participants Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
PFS Based on Investigator Assessment-Part A	224 Days Interval 172.0 to 419.0	70 Days Interval 47.0 to 115.0

SECONDARY outcome

Timeframe: Baseline up to approximately 9 years 7 months

Population: FAS included all patients assigned to study treatment.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=142 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
PFS Based on Investigator Assessment-Part B	10.8 Months Interval 7.2 to 12.8	—

SECONDARY outcome

Timeframe: Baseline up to approximately 6 years

Population: FAS included all patients assigned to study treatment.

OS was defined as the time (in days) from the date of first administration of study treatment to death due to any cause. Patients who were alive at the date of the LPLV were censored at the minimum of the date of LPLV and the last available date of evidence that the patient was still alive.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=33 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL n=51 Participants Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
Overall Survival (OS)-Part A	657 Days Interval 391.0 to NA: Value cannot be estimated due to censored data	211 Days Interval 140.0 to 399.0

SECONDARY outcome

Timeframe: Baseline up to approximately 9 years 7 months

Population: FAS included all patients assigned to study treatment.

OS was defined as the time (in days) from the date of first administration of study treatment to death due to any cause. OS was defined as the time (in days) from the date of first administration of study treatment to death due to any cause. Patients who were alive at the date of the LPLV were censored at the minimum of the date of LPLV and the last available date of evidence that the patient was still alive.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=142 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
OS-Part B	59.1 Months Interval 36.5 to NA: Value cannot be estimated due to censored data	—

SECONDARY outcome

Timeframe: Baseline up to week 16

Population: FAS included all patients assigned to study treatment. The analysis was performed by using last observation carried forward (LOCF) method.

HRQoL assessment was used to describe development of patients with copanlisib by using FACT-Lym questionnaire assessment tool. It contains 42 items (questions) covering HRQoL, common lymphoma symptoms and treatment side-effects. The FACT - General (FACT-G) questionnaire contains 27 items covering 4 core HRQoL subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 items) (FACT-Lym LymS), addressing issues typically experienced by lymphoma patients. Some of the issues covered include pain, itching, night sweats, trouble sleeping, fatigue and trouble concentrating. FACT-Lym also asks patients about lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment. Score range for the FACT-Lym LymS was 0 - 60, higher score represent less symptoms. Here in below table "n" signifies evaluable participants for the respective category.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=141 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
Functional Assessment of Cancer Therapy - Lymphoma Lymphoma Subscale (FACT-Lym LymS) at Week 16 - Part B Baseline	46.50 units on a scale Interval 40.5 to 52.0	—
Functional Assessment of Cancer Therapy - Lymphoma Lymphoma Subscale (FACT-Lym LymS) at Week 16 - Part B Value at Week 16	49.00 units on a scale Interval 42.0 to 54.0	—

SECONDARY outcome

Timeframe: Baseline up to week 16

Population: FAS included all patients assigned to study treatment. The analysis was performed by using last LOCF method.

HRQoL assessment was used to describe development of patients with copanlisib by using FACT-Lym questionnaire assessment tool. It contains 42 items (questions) covering HRQoL, common lymphoma symptoms and treatment side-effects. The FACT - General (FACT-G) questionnaire contains 27 items covering 4 core HRQoL subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 items) (FACT-Lym LymS), addressing issues typically experienced by lymphoma patients. Some of the issues covered include pain, itching, night sweats, trouble sleeping, fatigue and trouble concentrating. FACT-Lym also asks patients about lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment. FACT-Lym total score range was 0-168, higher score indicates better HRQoL. Here, in the below table "n" signifies evaluable participants for the respective category.

Outcome measures

Outcome measures
Measure	Part A: Indolent NHL/CLL n=141 Participants Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia \[iNHL/CLL\] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.	Part A: Aggressive NHL Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study.
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Total Score at Week 16 - Part B Baseline	127.50 units on a scale Interval 113.75 to 145.75	—
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Total Score at Week 16 - Part B Value at Week 16	130.83 units on a scale Interval 113.33 to 146.5	—

Adverse Events

Part A: Indolent NHL/CLL

Serious events: 16 serious events

Other events: 33 other events

Deaths: 21 deaths

Part A: Aggressive NHL

Serious events: 31 serious events

Other events: 50 other events

Deaths: 39 deaths

Part B: Indolent NHL

Serious events: 81 serious events

Other events: 138 other events

Deaths: 75 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

Bayer

Phone: +1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Contract Partners (PI) shall provide to Bayer any proposed publication or oral presentation relating to the Study or the Results ("Publication") at least sixty (60) days prior to the intended submission or presentation of the Publication in order to allow Bayer to review it. If Bayer does not notify PI within forty-five (45) days of Bayer's receipt of the intended Publication, PI shall remind Bayer. If Bayer does not provide any comments within the sixty day period, PI shall be free to publish.
Publication restrictions are in place

Restriction type: OTHER