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

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.

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

Study Overview

• Status: Completed
• Conditions: Diffuse, Large B-Cell, Lymphoma
• Intervention / Treatment: Drug: Copanlisib (Aliqopa, BAY80-6946)

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
  • Victoria
    • Ballarat, Victoria, Australia, 3350
    • Prahran, Victoria, Australia, 3181
• Belgium
  • Bruxelles - Brussel, Belgium, 1200
  • Edegem, Belgium, 2650
  • Gent, Belgium, 9000
  • Leuven, Belgium, 3000
  • Antwerpen
    • Wilrijk, Antwerpen, Belgium, 2610
• Canada
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
    • Montreal, Quebec, Canada, H3T 1E2
    • Sherbrooke, Quebec, Canada, J1H 5N4
• Denmark
  • Aarhus C, Denmark, 8000
  • Odense C, Denmark, 5000
• France
  • Caen Cedex, France, 14033
  • Creteil, France, 94010
  • Lille, France, 59037
  • PARIS cedex, France, 75475
  • POITIERS cedex, France, 86021
  • Pierre Benite, France, 69310
• Germany
  • Berlin, Germany, 10967
  • Nordrhein-Westfalen
    • Münster, Nordrhein-Westfalen, Germany, 48149
  • Sachsen
    • Leipzig, Sachsen, Germany
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20089
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
  • Seoul, Korea, Republic of, 05505
• Singapore
  • Singapore, Singapore, 169610
• United Kingdom
  • London, United Kingdom, NW1 2PG
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) in Total Population Based on Investigator Assessment	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.	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)
ORR by CD79b Status Based on Investigator Assessment	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.	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)
ORR by DLBCL/COO Subtype Based on Investigator Assessment	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.	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) in Total Population	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.	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
DOR by CD79b Status	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.	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
DOR by DLBCL/COO Subtype	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.	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
Progression-free Survival (PFS) in Total Population	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.	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
PFS by CD79b Status	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.	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
PFS by DLBCL/COO Subtype	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.	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
Overall Survival (OS) in Total Population	The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.	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
OS by CD79b Status	The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.	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
OS by DLBCL/COO Subtype	The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.	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
Duration of Stable Disease (DOSD) in Total Population	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.	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
Disease Control Rate (DCR) in Total Population	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.	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
DCR by CD79b Status	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.	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
DCR by DLBCL/COO Subtype	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.	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
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	A TEAE was defined as any event arising or worsening after the start of study drug administration until 30 days after the last application.	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Response (TTR) in Total Population	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.	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
ORR in Total Population Based on Central Imaging Review	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.	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)
ORR by CD79b Status Based on Central Imaging Review	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.	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)
ORR by DLBCL/COO Subtype Based on Central Imaging Review	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.	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)

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Lenz G, Hawkes E, Verhoef G, Haioun C, Thye Lim S, Seog Heo D, Ardeshna K, Chong G, Haaber J, Shi W, Gorbatchevsky I, Lippert S, Hiemeyer F, Piraino P, Beckmann G, Pena C, Buvaylo V, Childs BH, Salles G. Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma. Leukemia. 2020 Aug;34(8):2184-2197. doi: 10.1038/s41375-020-0743-y. Epub 2020 Feb 14.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2015
• Primary Completion (Actual): July 5, 2016
• Study Completion (Actual): January 19, 2018

Study Registration Dates

• First Submitted: February 16, 2015
• First Submitted That Met QC Criteria: March 11, 2015
• First Posted (Estimate): March 18, 2015

Study Record Updates

• Last Update Posted (Actual): January 4, 2019
• Last Update Submitted That Met QC Criteria: December 10, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: 17119; 2014-004848-36 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No