Trial Outcomes & Findings for Phase III Copanlisib in Rituximab-refractory iNHL (NCT NCT02369016)

Last Updated: 2023-11-18

Results Overview

Adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

25 participants

Primary outcome timeframe

up to 7 years

Results posted on

2023-11-18

Participant Flow

The study was conducted at 20 study centers in 10 countries/regions: Brazil (2), Bulgaria (1), Greece (1), Italy (2), Poland (1), Russian Federation (5), South Africa (1), South Korea (5), Taiwan (1) and Turkey (1) between 22 September 2015 (first patient first visit) and 26 October 2022 (last patient last visit).

34 participants were screened. 9 participants were screening failures and 25 participants were randomized to study treatment: 17 to copanlisib and 8 to placebo. All randomized participants also received at least one dose of study treatment and were valid for safety analyses. After study unblinding 7 placebo participants switched to copanlisib.

Participant milestones

Participant milestones
Measure	Copanlisib (BAY80-6946, Aliqopa) Participants who were randomized to copanlisib until end of the study	Placebo Participants who were randomized to placebo until switching from placebo to copanlsib after disease progression or after study unblinding
Overall Study STARTED	17	8
Overall Study Switched to Copanlisib After Study Unblinding	0	7
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	17	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Copanlisib (BAY80-6946, Aliqopa) Participants who were randomized to copanlisib until end of the study	Placebo Participants who were randomized to placebo until switching from placebo to copanlsib after disease progression or after study unblinding
Overall Study AE associated with clinical disease progression	2	1
Overall Study AE not associated with clinical diseaseprogression	4	1
Overall Study Progressive disease - clinical progression	1	4
Overall Study withdrawal by patient	4	0
Overall Study Progressive disease - radiological progression	6	2

Baseline Characteristics

Phase III Copanlisib in Rituximab-refractory iNHL

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Copanlisib (BAY80-6946, Aliqopa) n=17 Participants Participants who were randomized to copanlisib until end of the study	Placebo n=8 Participants Participants who were randomized to placebo until switching from placebo to copanlisib after disease progression or after study unblinding	Total n=25 Participants Total of all reporting groups
Age, Customized Adults (18-64 years)	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Age, Customized From 65-84 years	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 7 years

Adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)

Outcome measures

Outcome measures
Measure	Copanlisib (BAY80-6946, Aliqopa) n=17 Participants Participants who were randomized to copanlisib until end of the study	Placebo n=8 Participants Participants who were randomized to placebo until switching from placebo to copanlsib after disease progression or after study unblinding	Switched to Copanlisib n=7 Participants Participants who switched from placebo to copanlisib	Treated With Copanlisib n=24 Participants Participants who were treated with copanlisib (randomized to copanlisib + switched from placebo to copanlisib)
Number of Participants With Treatment-emergent Adverse Events (TEAE)s	17 Participants	7 Participants	7 Participants	24 Participants

PRIMARY outcome

Timeframe: up to 7 years

Serious adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)

Outcome measures

Outcome measures
Measure	Copanlisib (BAY80-6946, Aliqopa) n=17 Participants Participants who were randomized to copanlisib until end of the study	Placebo n=8 Participants Participants who were randomized to placebo until switching from placebo to copanlsib after disease progression or after study unblinding	Switched to Copanlisib n=7 Participants Participants who switched from placebo to copanlisib	Treated With Copanlisib n=24 Participants Participants who were treated with copanlisib (randomized to copanlisib + switched from placebo to copanlisib)
Number of Participants With Treatment-emergent Serious Adverse Events (TESAE)s	6 Participants	1 Participants	5 Participants	11 Participants

PRIMARY outcome

Timeframe: up to 7 years

\- Above threshold of 10% and reported as TEAEs - any event (Grade 1-4)

Outcome measures

Outcome measures
Measure	Copanlisib (BAY80-6946, Aliqopa) n=17 Participants Participants who were randomized to copanlisib until end of the study	Placebo n=8 Participants Participants who were randomized to placebo until switching from placebo to copanlsib after disease progression or after study unblinding	Switched to Copanlisib n=7 Participants Participants who switched from placebo to copanlisib	Treated With Copanlisib n=24 Participants Participants who were treated with copanlisib (randomized to copanlisib + switched from placebo to copanlisib)
Number of Participants With Abnormal Laboratory Parameters Neutropenia	6 Participants	0 Participants	1 Participants	7 Participants
Number of Participants With Abnormal Laboratory Parameters Neutrophil count decreased	4 Participants	0 Participants	2 Participants	6 Participants
Number of Participants With Abnormal Laboratory Parameters Anaemia	2 Participants	2 Participants	4 Participants	6 Participants
Number of Participants With Abnormal Laboratory Parameters ANY	9 Participants	1 Participants	3 Participants	12 Participants
Number of Participants With Abnormal Laboratory Parameters Hyperglycaemia	6 Participants	0 Participants	4 Participants	10 Participants
Number of Participants With Abnormal Laboratory Parameters Platelet count decreased	3 Participants	0 Participants	2 Participants	5 Participants

PRIMARY outcome

Timeframe: up to 7 years

\- Reported as TEAEs - worst CTCAE grade total -

Outcome measures

Outcome measures
Measure	Copanlisib (BAY80-6946, Aliqopa) n=17 Participants Participants who were randomized to copanlisib until end of the study	Placebo n=8 Participants Participants who were randomized to placebo until switching from placebo to copanlsib after disease progression or after study unblinding	Switched to Copanlisib n=7 Participants Participants who switched from placebo to copanlisib	Treated With Copanlisib n=24 Participants Participants who were treated with copanlisib (randomized to copanlisib + switched from placebo to copanlisib)
Number of Participants With Abnormal Vital Signs Blood pressure increased	2 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With Abnormal Vital Signs Electrocardiogram QT prolonged	1 Participants	0 Participants	0 Participants	1 Participants

Adverse Events

Randomized to Copanlisib

Serious events: 6 serious events

Other events: 17 other events

Deaths: 2 deaths

Randomized to Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 1 deaths

Switched to Copanlisib

Serious events: 5 serious events

Other events: 7 other events

Deaths: 2 deaths

Treated With Copanlisib

Serious events: 11 serious events

Other events: 24 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Randomized to Copanlisib n=17 participants at risk Participants who were randomized to copanlisib until end of the study	Randomized to Placebo n=8 participants at risk Participants who were randomized to placebo until switching from placebo to copanlsib after disease progression or after study unblinding	Switched to Copanlisib n=7 participants at risk Participants who switched from placebo to copanlisib	Treated With Copanlisib n=24 participants at risk Participants who were treated with copanlisib (randomized to copanlisib + switched from placebo to copanlisib)
Gastrointestinal disorders Diarrhoea	5.9% 1/17 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/8 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/7 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	4.2% 1/24 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years
General disorders General physical health deterioration	5.9% 1/17 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/8 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/7 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	4.2% 1/24 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years
Infections and infestations Pneumonia	5.9% 1/17 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/8 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	28.6% 2/7 • Number of events 3 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	12.5% 3/24 • Number of events 4 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years
Infections and infestations Cellulitis	5.9% 1/17 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/8 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/7 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	4.2% 1/24 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years
Infections and infestations Klebsiella bacteraemia	0.00% 0/17 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/8 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	14.3% 1/7 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	4.2% 1/24 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years
Investigations Alanine aminotransferase increased	5.9% 1/17 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/8 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/7 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	4.2% 1/24 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years
Investigations Aspartate aminotransferase increased	5.9% 1/17 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/8 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/7 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	4.2% 1/24 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years
Infections and infestations Pneumocystis jirovecii pneumonia	5.9% 1/17 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/8 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/7 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	4.2% 1/24 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/17 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/8 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	14.3% 1/7 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	4.2% 1/24 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years
Metabolism and nutrition disorders Hyperglycaemic hyperosmolar nonketotic syndrome	0.00% 0/17 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/8 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	14.3% 1/7 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	4.2% 1/24 • Number of events 1 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/17 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	12.5% 1/8 • Number of events 2 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/7 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years	0.00% 0/24 • from the start of study drug administration until 30 days after the last study drug administraion, up to end of safety follow-up, approximately 7 years

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
Publication restrictions are in place

Restriction type: OTHER