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

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02391116
• Collaborator: (none)
• Enrollment: 67
• Locations: 32
• Arm: 1
• Actual Duration (Months): 32.4
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To assess the potential efficacy (in terms of objective response) of single agent copanlisib in patients with relapsed or refractory Diffuse large B-cell lymphoma (DLBCL) and assess the relationship between efficacy and a potentially predictive biomarker

Condition or Disease	Intervention/Treatment	Phase
Diffuse, Large B-Cell, Lymphoma	Drug: Copanlisib (Aliqopa, BAY80-6946)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 67 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Single-arm Phase II Study in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) to Evaluate Efficacy and Safety of Treatment With Single Agent Copanlisib and the Impact of Biomarkers Thereupon.
• Actual Study Start Date: May 8, 2015
• Actual Primary Completion Date: Jul 5, 2016
• Actual Study Completion Date: Jan 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Copanlisib (Aliqopa, BAY80-6946) Copanlisib (Aliqopa, BAY80-6946) solution for IV infusion (test drug/investigational medicinal product)	Drug: Copanlisib (Aliqopa, BAY80-6946); 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

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) in Total Population Based on Investigator Assessment [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)]

   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.

2. ORR by CD79b Status Based on Investigator Assessment [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)]

   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.

3. ORR by DLBCL/COO Subtype Based on Investigator Assessment [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)]

   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.

Secondary Outcome Measures

1. Duration of Response (DOR) in Total Population [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]

   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.

2. DOR by CD79b Status [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]

   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.

3. DOR by DLBCL/COO Subtype [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]

   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.

4. Progression-free Survival (PFS) in Total Population [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]

   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.

5. PFS by CD79b Status [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]

   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.

6. PFS by DLBCL/COO Subtype [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]

   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.

7. Overall Survival (OS) in Total Population [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]

   The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.

8. OS by CD79b Status [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]

   The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.

9. OS by DLBCL/COO Subtype [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]

   The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.

10. Duration of Stable Disease (DOSD) in Total Population [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]

    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.

11. Disease Control Rate (DCR) in Total Population [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]

    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.

12. DCR by CD79b Status [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]

    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.

13. DCR by DLBCL/COO Subtype [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]

    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.

14. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [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]

    A TEAE was defined as any event arising or worsening after the start of study drug administration until 30 days after the last application.

Other Outcome Measures

1. Time to Response (TTR) in Total Population [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]

   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.

2. ORR in Total Population Based on Central Imaging Review [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)]

   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.

3. ORR by CD79b Status Based on Central Imaging Review [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)]

   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.

4. ORR by DLBCL/COO Subtype Based on Central Imaging Review [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)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of Diffuse large B-cell lymphoma (DLBCL) (de novo or DLBCL transformed from follicular lymphoma on the basis of a tissue biopsy).

• Received at least one prior therapy for aggressive Non-Hodgkin's Lymphoma (NHL) (DLBCL).

• Received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) + rituximab or equivalent regimen.

• Patients must have measurable disease.

• Not eligible or not willing to receive the high-dose (myeloablative) chemotherapy (HDC) and stem cell transplant (SCT).

• A fresh tumor biopsy collected during screening and /or archival tumor tissue collected after the last relapse/disease progression.

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.

• Left ventricular ejection fraction (LVEF) ≥ the lower limit of normal (LLN) for the Institution. (as per local standard of care) as measured by echocardiogram (ECHO) or Multiple gated acquisition (MUGA) scan.

• Adequate bone marrow, liver and renal function.

Exclusion Criteria:

• Any of the following as the only site(s) of disease: palpable lymph nodes not visible on imaging studies, skin lesions, or bone marrow involvement only.

• Active CTCAE (Common Terminology Criteria for Adverse Events) Grade 3/4 infection.

• Current central nervous system (CNS) involvement by lymphoma.

• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction within the past 6 months before start of study treatment.

• Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion).

• Type I or II diabetes mellitus with HbA1c > 8.5% at Screening.

• New York Heart Association (NYHA) class III or IV heart disease.

• History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator).

• Patients who previously received therapy with copanlisib or other PI3K inhibitors are not eligible for enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Kingswood	New South Wales	Australia	2747
2		Ballarat	Victoria	Australia	3350
3		Prahran	Victoria	Australia	3181
4		Box Hill		Australia	3128
5		Wilrijk	Antwerpen	Belgium	2610
6		Bruxelles - Brussel		Belgium	1200
7		Edegem		Belgium	2650
8		Gent		Belgium	9000
9		Leuven		Belgium	3000
10		St. John's	Newfoundland and Labrador	Canada	A1B 3V6
11		Brampton	Ontario	Canada	L6R 3J7
12		Montreal	Quebec	Canada	H1T 2M4
13		Montreal	Quebec	Canada	H3T 1E2
14		Sherbrooke	Quebec	Canada	J1H 5N4
15		Aarhus C		Denmark	8000
16		Odense C		Denmark	5000
17		Caen Cedex		France	14033
18		Creteil		France	94010
19		Lille		France	59037
20		PARIS cedex		France	75475
21		Pierre Benite		France	69310
22		POITIERS cedex		France	86021
23		Münster	Nordrhein-Westfalen	Germany	48149
24		Leipzig	Sachsen	Germany
25		Berlin		Germany	10967
26		Milano	Lombardia	Italy	20089
27		Seoul		Korea, Republic of	05505
28		Seoul		Korea, Republic of	110-744
29		Singapore		Singapore	169610
30		Truro	Cornwall	United Kingdom	TR1 3LJ
31		Southampton	Hampshire	United Kingdom	SO16 6YD
32		London		United Kingdom	NW1 2PG

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here to find results for studies related to Bayer products.

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02391116
• Other Study ID Numbers: 17119; 2014-004848-36
• First Posted: Mar 18, 2015
• Last Update Posted: Jan 4, 2019
• Last Verified: Dec 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse

Study Results

Participant Flow

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 Detail	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)
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
NOT COMPLETED	14
Period Title: Treatment
STARTED	56
COMPLETED	43
NOT COMPLETED	13
Period Title: Treatment
STARTED	9
COMPLETED	6
NOT COMPLETED	3
Period Title: Treatment
STARTED	46
COMPLETED	42
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Copanlisib (Aliqopa, BAY80-6946)
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 Participants	67
Age (Years) [Mean (Standard Deviation) ]
Full analysis set (FAS)	65.3 (14.5)
Per protocol set (PPS)	69.2 (12.2)
Sex: Female, Male (Count of Participants)
Female	28 41.8%
Male	39 58.2%
Female	15 22.4%
Male	25 37.3%
CD79b Status (Count of Participants)
CD79b Mutant	9 13.4%
CD79b Wild-type	45 67.2%
CD79b Status Missing	13 19.4%
CD79b Mutant	8 11.9%
CD79b Wild-type	32 47.8%
CD79b Status Missing	0 0%
DLBCL / Cell of Origin (COO) Subtype (Count of 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%
Activated B-cell-like (ABC)	16 23.9%
Germinal center B-cell-like (GCB)	22 32.8%
Unclassifiable	2 3%
DLBCL/COO Subtype Missing	0 0%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) in Total Population Based on Investigator Assessment
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)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) and per protocol set (PPS)

Arm/Group Title	Copanlisib (Aliqopa, BAY80-6946)
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
Measure Participants	67
Full analysis set (FAS)	19.4 29%
Per protocol set (PPS)	25.0 37.3%

2. Primary Outcome

Title	ORR by CD79b Status Based on Investigator Assessment
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)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) and per protocol set (PPS)

Arm/Group Title	CD79b Mutant	CD79b Wild-type	CD79b Status Missing
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
Measure Participants	9	45	13
Full analysis set (FAS)	22.2 33.1%	20.0 NaN	15.4 NaN
Per protocol set (PPS)	25.0 37.3%	25.0 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Copanlisib (Aliqopa, BAY80-6946), CD79b Wild-type
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 90%; -28.7 to 32.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	ORR difference in FAS (N=54): ORR in CD79b mutant subgroup minus ORR in CD79b wild-type subgroup

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Copanlisib (Aliqopa, BAY80-6946), CD79b Wild-type
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 90%; -33.5 to 33.5
	Parameter Dispersion	Type: Value:
	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
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)

Outcome Measure Data

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
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
Measure Participants	19	30	3	15
Full analysis set (FAS)	31.6 47.2%	13.3 NaN	33.3 NaN	13.3 NaN
Per protocol set (PPS)	37.5 56%	13.6 NaN	50.0 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Copanlisib (Aliqopa, BAY80-6946), CD79b Wild-type, CD79b Status Missing
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	16.4
	Confidence Interval	(2-Sided) 90%; -7.2 to 39.1
	Parameter Dispersion	Type: Value:
	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)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Copanlisib (Aliqopa, BAY80-6946), CD79b Wild-type, CD79b Status Missing
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	20.8
	Confidence Interval	(2-Sided) 90%; -6.8 to 46.2
	Parameter Dispersion	Type: Value:
	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)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Copanlisib (Aliqopa, BAY80-6946), CD79b Wild-type, CD79b Status Missing
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-18.5
	Confidence Interval	(2-Sided) 90%; -40.1 to 4.6
	Parameter Dispersion	Type: Value:
	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)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Copanlisib (Aliqopa, BAY80-6946), CD79b Wild-type, CD79b Status Missing
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-25.3
	Confidence Interval	(2-Sided) 90%; -49.1 to 1.1
	Parameter Dispersion	Type: Value:
	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)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Copanlisib (Aliqopa, BAY80-6946), CD79b Wild-type, CD79b Status Missing
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	12.9
	Confidence Interval	(2-Sided) 90%; -42.4 to 63.2
	Parameter Dispersion	Type: Value:
	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)

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Copanlisib (Aliqopa, BAY80-6946), CD79b Wild-type, CD79b Status Missing
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	26.3
	Confidence Interval	(2-Sided) 90%; -44.3 to 77.6
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

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)
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
Measure Participants	13
Median (95% Confidence Interval) [Days]	132

5. Secondary Outcome

Title	DOR by CD79b Status
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

Outcome Measure Data

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
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
Measure Participants	2	9	2
Median (95% Confidence Interval) [Days]	516	113	113

6. Secondary Outcome

Title	DOR by DLBCL/COO Subtype
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

Outcome Measure Data

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
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
Measure Participants	6	4	1	2
Median (95% Confidence Interval) [Days]	193	183	52	113

7. Secondary Outcome

Title	Progression-free Survival (PFS) in Total Population
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

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Copanlisib (Aliqopa, BAY80-6946)
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
Measure Participants	67
Median (95% Confidence Interval) [Days]	54

8. Secondary Outcome

Title	PFS by CD79b Status
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

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	CD79b Mutant	CD79b Wild-type	CD79b Status Missing
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
Measure Participants	9	45	13
Median (95% Confidence Interval) [Days]	73	52	56

9. Secondary Outcome

Title	PFS by DLBCL/COO Subtype
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

Outcome Measure Data

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
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
Measure Participants	19	30	3	15
Median (95% Confidence Interval) [Days]	73	52	84	51

10. Secondary Outcome

Title	Overall Survival (OS) in Total Population
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

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Copanlisib (Aliqopa, BAY80-6946)
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
Measure Participants	67
Median (95% Confidence Interval) [Days]	224

11. Secondary Outcome

Title	OS by CD79b Status
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

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	CD79b Mutant	CD79b Wild-type	CD79b Status Missing
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
Measure Participants	9	45	13
Median (95% Confidence Interval) [Days]	178	242	224

12. Secondary Outcome

Title	OS by DLBCL/COO Subtype
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

Outcome Measure Data

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
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
Measure Participants	19	30	3	15
Median (95% Confidence Interval) [Days]	210	287	164	160

13. Secondary Outcome

Title	Duration of Stable Disease (DOSD) in Total Population
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

Outcome Measure Data

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)
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
Measure Participants	14
Median (95% Confidence Interval) [Days]	106

14. Secondary Outcome

Title	Disease Control Rate (DCR) in Total Population
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

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Copanlisib (Aliqopa, BAY80-6946)
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
Measure Participants	67
Number (90% Confidence Interval) [Percentage of participants]	40.3 60.1%

15. Secondary Outcome

Title	DCR by CD79b Status
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

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	CD79b Mutant	CD79b Wild-type	CD79b Status Missing
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
Measure Participants	9	45	13
Number (90% Confidence Interval) [Percentage of participants]	55.6 83%	40.0 NaN	30.8 NaN

16. Secondary Outcome

Title	DCR by DLBCL/COO Subtype
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

Outcome Measure Data

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
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
Measure Participants	19	30	3	15
Number (90% Confidence Interval) [Percentage of participants]	52.6 78.5%	40.0 NaN	33.3 NaN	26.7 NaN

17. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
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

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAF)

Arm/Group Title	Copanlisib (Aliqopa, BAY80-6946)
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
Measure Participants	67
Any TEAE	65 97%
Any TESAE	44 65.7%

18. Other Pre-specified Outcome

Title	Time to Response (TTR) in Total Population
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

Outcome Measure Data

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)
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
Measure Participants	13
Median (95% Confidence Interval) [Days]	52

19. Other Pre-specified Outcome

Title	ORR in Total Population Based on Central Imaging Review
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Copanlisib (Aliqopa, BAY80-6946)
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
Measure Participants	67
Number (90% Confidence Interval) [Percentage of participants]	22.4 33.4%

20. Other Pre-specified Outcome

Title	ORR by CD79b Status Based on Central Imaging Review
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)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	CD79b Mutant	CD79b Wild-type	CD79b Status Missing
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
Measure Participants	9	45	13
Number (90% Confidence Interval) [Percentage of participants]	44.4 66.3%	20.0 NaN	15.4 NaN

21. Other Pre-specified Outcome

Title	ORR by DLBCL/COO Subtype Based on Central Imaging Review
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)

Outcome Measure Data

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
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
Measure Participants	19	30	3	15
Number (90% Confidence Interval) [Percentage of participants]	47.4 70.7%	13.3 NaN	0.0 NaN	13.3 NaN

Adverse Events

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
Arm/Group Title	Copanlisib (Aliqopa, BAY80-6946)
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 (%)	# Events
Total	53/67 (79.1%)
Serious Adverse Events
	Copanlisib (Aliqopa, BAY80-6946)
	Affected / at Risk (%)	# Events
Total	44/67 (65.7%)
Blood and lymphatic system disorders
Febrile neutropenia	1/67 (1.5%)	1
Lymphadenopathy	1/67 (1.5%)	1
Thrombocytopenia	1/67 (1.5%)	1
Eye disorders
Diplopia	1/67 (1.5%)	1
Gastrointestinal disorders
Abdominal pain	3/67 (4.5%)	3
Colitis	1/67 (1.5%)	1
Gastrointestinal haemorrhage	1/67 (1.5%)	1
Nausea	1/67 (1.5%)	1
Vomiting	1/67 (1.5%)	3
General disorders
Asthenia	1/67 (1.5%)	1
Death	2/67 (3%)	2
Fatigue	1/67 (1.5%)	1
Pyrexia	4/67 (6%)	4
Sudden death	1/67 (1.5%)	1
General physical health deterioration	9/67 (13.4%)	9
Infections and infestations
Cystitis	1/67 (1.5%)	1
Herpes zoster	1/67 (1.5%)	1
Lower respiratory tract infection	1/67 (1.5%)	1
Pneumonia pneumococcal	1/67 (1.5%)	1
Thrombophlebitis septic	1/67 (1.5%)	1
Urosepsis	1/67 (1.5%)	1
Escherichia urinary tract infection	1/67 (1.5%)	1
Lung infection	2/67 (3%)	3
Respiratory tract infection viral	1/67 (1.5%)	1
Splenic infection fungal	1/67 (1.5%)	1
Hepatic infection fungal	1/67 (1.5%)	1
Pneumocystis jirovecii pneumonia	1/67 (1.5%)	1
Investigations
Amylase increased	1/67 (1.5%)	1
Blood creatinine increased	1/67 (1.5%)	1
Lipase increased	1/67 (1.5%)	1
Neutrophil count decreased	1/67 (1.5%)	1
Metabolism and nutrition disorders
Cachexia	1/67 (1.5%)	1
Dehydration	1/67 (1.5%)	1
Hypercalcaemia	1/67 (1.5%)	1
Hyperglycaemia	5/67 (7.5%)	5
Hyponatraemia	1/67 (1.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/67 (3%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Inflammatory carcinoma of the breast	1/67 (1.5%)	1
Mycosis fungoides	1/67 (1.5%)	1
Cancer pain	1/67 (1.5%)	1
Nervous system disorders
Neurological symptom	1/67 (1.5%)	1
Renal and urinary disorders
Haematuria	1/67 (1.5%)	1
Renal failure	1/67 (1.5%)	1
Urinary retention	1/67 (1.5%)	1
Acute kidney injury	1/67 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/67 (1.5%)	1
Cough	1/67 (1.5%)	1
Dyspnoea	2/67 (3%)	2
Pleural effusion	2/67 (3%)	2
Pneumonitis	3/67 (4.5%)	3
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome	1/67 (1.5%)	1
Vascular disorders
Hypertension	1/67 (1.5%)	1
Deep vein thrombosis	1/67 (1.5%)	1
Other (Not Including Serious) Adverse Events
	Copanlisib (Aliqopa, BAY80-6946)
	Affected / at Risk (%)	# Events
Total	64/67 (95.5%)
Blood and lymphatic system disorders
Anaemia	6/67 (9%)	6
Neutropenia	9/67 (13.4%)	9
Thrombocytopenia	6/67 (9%)	6
Cardiac disorders
Tachycardia	3/67 (4.5%)	3
Gastrointestinal disorders
Abdominal pain	5/67 (7.5%)	5
Constipation	11/67 (16.4%)	11
Diarrhoea	25/67 (37.3%)	38
Mouth ulceration	8/67 (11.9%)	8
Nausea	20/67 (29.9%)	23
Stomatitis	5/67 (7.5%)	5
Vomiting	12/67 (17.9%)	13
Paraesthesia oral	3/67 (4.5%)	5
General disorders
Asthenia	3/67 (4.5%)	3
Chest pain	3/67 (4.5%)	3
Chills	3/67 (4.5%)	3
Fatigue	18/67 (26.9%)	19
Mucosal inflammation	4/67 (6%)	4
Oedema peripheral	7/67 (10.4%)	7
Pyrexia	12/67 (17.9%)	12
Infections and infestations
Upper respiratory tract infection	4/67 (6%)	4
Injury, poisoning and procedural complications
Fall	3/67 (4.5%)	4
Investigations
Lipase increased	3/67 (4.5%)	3
Lymphocyte count decreased	3/67 (4.5%)	4
Platelet count decreased	5/67 (7.5%)	5
Weight decreased	3/67 (4.5%)	3
White blood cell count decreased	3/67 (4.5%)	3
Metabolism and nutrition disorders
Hyperglycaemia	21/67 (31.3%)	27
Hypoglycaemia	3/67 (4.5%)	3
Hypokalaemia	8/67 (11.9%)	15
Hyponatraemia	4/67 (6%)	6
Hypophosphataemia	3/67 (4.5%)	4
Decreased appetite	10/67 (14.9%)	14
Musculoskeletal and connective tissue disorders
Arthralgia	4/67 (6%)	4
Muscle spasms	6/67 (9%)	7
Pain in extremity	3/67 (4.5%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	4/67 (6%)	4
Nervous system disorders
Dizziness	4/67 (6%)	6
Headache	9/67 (13.4%)	9
Paraesthesia	4/67 (6%)	6
Psychiatric disorders
Insomnia	3/67 (4.5%)	3
Respiratory, thoracic and mediastinal disorders
Cough	12/67 (17.9%)	12
Dyspnoea	5/67 (7.5%)	5
Productive cough	4/67 (6%)	4
Oropharyngeal pain	3/67 (4.5%)	3
Skin and subcutaneous tissue disorders
Dry skin	6/67 (9%)	7
Rash	9/67 (13.4%)	10
Vascular disorders
Haematoma	3/67 (4.5%)	3
Hypertension	27/67 (40.3%)	42
Hypotension	3/67 (4.5%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.