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

Study Overview
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Brief Summary
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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

Official Title
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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.

Conditions
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Diffuse, Large B-Cell, Lymphoma

Intervention / Treatment
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* Drug: Copanlisib (Aliqopa, BAY80-6946)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Copanlisib (Aliqopa, BAY80-6946)<br>Copanlisib (Aliqopa, BAY80-6946) solution for IV infusion (test drug/investigational medicinal product) | Drug: Copanlisib (Aliqopa, BAY80-6946)<br>* 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<br>|

What is the study measuring?
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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 |