Diffuse, Large B-Cell, Lymphoma
Conditions
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
Interventions
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
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Italy, Singapore, South Korea, United Kingdom
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 67 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Active Follow-up | Switching to Other Therapy | 2 |
| Active Follow-up | Withdrawal by Subject | 1 |
| Safety Follow-up | Adverse Event | 1 |
| Safety Follow-up | Deterioration of General Conditions | 3 |
| Safety Follow-up | No Follow Up | 1 |
| Safety Follow-up | Switching to Other Therapy | 4 |
| Safety Follow-up | Withdrawal by Subject | 4 |
| Survival Follow-up | Switching to Other Therapy | 1 |
| Survival Follow-up | Withdrawal by Subject | 3 |
| Treatment | Adverse Event (AE) Without Clinical PD | 9 |
| Treatment | AE with Clinical PD | 3 |
| Treatment | Protocol Violation | 1 |
| Treatment | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Copanlisib (Aliqopa, BAY80-6946) |
|---|---|
| Age, Continuous Full analysis set (FAS) | 65.3 Years STANDARD_DEVIATION 14.5 |
| Age, Continuous Per protocol set (PPS) | 69.2 Years STANDARD_DEVIATION 12.2 |
| CD79b Status Full analysis set (FAS) CD79b Mutant | 9 Participants |
| CD79b Status Full analysis set (FAS) CD79b Status Missing | 13 Participants |
| CD79b Status Full analysis set (FAS) CD79b Wild-type | 45 Participants |
| CD79b Status Per protocol set (PPS) CD79b Mutant | 8 Participants |
| CD79b Status Per protocol set (PPS) CD79b Status Missing | 0 Participants |
| CD79b Status Per protocol set (PPS) CD79b Wild-type | 32 Participants |
| DLBCL / Cell of Origin (COO) Subtype Full analysis set (FAS) Activated B-cell-like (ABC) | 19 Participants |
| DLBCL / Cell of Origin (COO) Subtype Full analysis set (FAS) DLBCL/COO Subtype Missing | 15 Participants |
| DLBCL / Cell of Origin (COO) Subtype Full analysis set (FAS) Germinal center B-cell-like (GCB) | 30 Participants |
| DLBCL / Cell of Origin (COO) Subtype Full analysis set (FAS) Unclassifiable | 3 Participants |
| DLBCL / Cell of Origin (COO) Subtype Per protocol set (PPS) Activated B-cell-like (ABC) | 16 Participants |
| DLBCL / Cell of Origin (COO) Subtype Per protocol set (PPS) DLBCL/COO Subtype Missing | 0 Participants |
| DLBCL / Cell of Origin (COO) Subtype Per protocol set (PPS) Germinal center B-cell-like (GCB) | 22 Participants |
| DLBCL / Cell of Origin (COO) Subtype Per protocol set (PPS) Unclassifiable | 2 Participants |
| Sex: Female, Male Full analysis set (FAS) Female | 28 Participants |
| Sex: Female, Male Full analysis set (FAS) Male | 39 Participants |
| Sex: Female, Male Per protocol set (PPS) Female | 15 Participants |
| Sex: Female, Male Per protocol set (PPS) Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 53 / 67 |
| other Total, other adverse events | 64 / 67 |
| serious Total, serious adverse events | 44 / 67 |
Outcome results
Primary
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.
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)
Population: Full analysis set (FAS) and per protocol set (PPS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | Objective Response Rate (ORR) in Total Population Based on Investigator Assessment | Full analysis set (FAS) | 19.4 Percentage of participants |
| Copanlisib (Aliqopa, BAY80-6946) | Objective Response Rate (ORR) in Total Population Based on Investigator Assessment | Per protocol set (PPS) | 25.0 Percentage of participants |
Primary
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.
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)
Population: Full analysis set (FAS) and per protocol set (PPS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | ORR by CD79b Status Based on Investigator Assessment | Full analysis set (FAS) | 22.2 Percentage of participants |
| Copanlisib (Aliqopa, BAY80-6946) | ORR by CD79b Status Based on Investigator Assessment | Per protocol set (PPS) | 25.0 Percentage of participants |
| CD79b Wild-type | ORR by CD79b Status Based on Investigator Assessment | Full analysis set (FAS) | 20.0 Percentage of participants |
| CD79b Wild-type | ORR by CD79b Status Based on Investigator Assessment | Per protocol set (PPS) | 25.0 Percentage of participants |
| CD79b Status Missing | ORR by CD79b Status Based on Investigator Assessment | Full analysis set (FAS) | 15.4 Percentage of participants |
90% CI: [-28.7, 32.9]Exact confidence intervals (CI)
90% CI: [-33.5, 33.5]Exact confidence intervals (CI)
Primary
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.
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)
Population: Full analysis set (FAS) and per protocol set (PPS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | ORR by DLBCL/COO Subtype Based on Investigator Assessment | Full analysis set (FAS) | 31.6 Percentage of participants |
| Copanlisib (Aliqopa, BAY80-6946) | ORR by DLBCL/COO Subtype Based on Investigator Assessment | Per protocol set (PPS) | 37.5 Percentage of participants |
| CD79b Wild-type | ORR by DLBCL/COO Subtype Based on Investigator Assessment | Full analysis set (FAS) | 13.3 Percentage of participants |
| CD79b Wild-type | ORR by DLBCL/COO Subtype Based on Investigator Assessment | Per protocol set (PPS) | 13.6 Percentage of participants |
| CD79b Status Missing | ORR by DLBCL/COO Subtype Based on Investigator Assessment | Full analysis set (FAS) | 33.3 Percentage of participants |
| CD79b Status Missing | ORR by DLBCL/COO Subtype Based on Investigator Assessment | Per protocol set (PPS) | 50.0 Percentage of participants |
| DLBCL/COO Subtype Missing | ORR by DLBCL/COO Subtype Based on Investigator Assessment | Full analysis set (FAS) | 13.3 Percentage of participants |
90% CI: [-7.2, 39.1]Exact confidence intervals (CI)
90% CI: [-6.8, 46.2]Exact confidence intervals (CI)
90% CI: [-40.1, 4.6]Exact confidence intervals (CI)
90% CI: [-49.1, 1.1]Exact confidence intervals (CI)
90% CI: [-42.4, 63.2]Exact confidence intervals (CI)
90% CI: [-44.3, 77.6]Exact confidence intervals (CI)
Secondary
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.
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
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | DCR by CD79b Status | 55.6 Percentage of participants |
| CD79b Wild-type | DCR by CD79b Status | 40.0 Percentage of participants |
| CD79b Status Missing | DCR by CD79b Status | 30.8 Percentage of participants |
Secondary
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.
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
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | DCR by DLBCL/COO Subtype | 52.6 Percentage of participants |
| CD79b Wild-type | DCR by DLBCL/COO Subtype | 40.0 Percentage of participants |
| CD79b Status Missing | DCR by DLBCL/COO Subtype | 33.3 Percentage of participants |
| DLBCL/COO Subtype Missing | DCR by DLBCL/COO Subtype | 26.7 Percentage of participants |
Secondary
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.
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
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | Disease Control Rate (DCR) in Total Population | 40.3 Percentage of participants |
Secondary
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.
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
Population: Responders (i.e. participants with a best response of CR or PR) in full analysis set based on the investigator assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | DOR by CD79b Status | 516 Days |
| CD79b Wild-type | DOR by CD79b Status | 113 Days |
| CD79b Status Missing | DOR by CD79b Status | 113 Days |
Secondary
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.
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
Population: Responders (i.e. participants with a best response of CR or PR) in full analysis set based on the investigator assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | DOR by DLBCL/COO Subtype | 193 Days |
| CD79b Wild-type | DOR by DLBCL/COO Subtype | 183 Days |
| CD79b Status Missing | DOR by DLBCL/COO Subtype | 52 Days |
| DLBCL/COO Subtype Missing | DOR by DLBCL/COO Subtype | 113 Days |
Secondary
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.
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
Population: Responders (i.e. participants with a best response of CR or PR) in full analysis set based on the investigator assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | Duration of Response (DOR) in Total Population | 132 Days |
Secondary
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.
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
Population: Participants who failed to achieve CR or PR but achieved SD in full analysis set based on the investigator assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | Duration of Stable Disease (DOSD) in Total Population | 106 Days |
Secondary
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.
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
Population: Safety analysis set (SAF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 65 Participants |
| Copanlisib (Aliqopa, BAY80-6946) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 44 Participants |
Secondary
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.
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
Population: Full analysis set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | OS by CD79b Status | 178 Days |
| CD79b Wild-type | OS by CD79b Status | 242 Days |
| CD79b Status Missing | OS by CD79b Status | 224 Days |
Secondary
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.
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
Population: Full analysis set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | OS by DLBCL/COO Subtype | 210 Days |
| CD79b Wild-type | OS by DLBCL/COO Subtype | 287 Days |
| CD79b Status Missing | OS by DLBCL/COO Subtype | 164 Days |
| DLBCL/COO Subtype Missing | OS by DLBCL/COO Subtype | 160 Days |
Secondary
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.
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
Population: Full analysis set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | Overall Survival (OS) in Total Population | 224 Days |
Secondary
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.
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
Population: Full analysis set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | PFS by CD79b Status | 73 Days |
| CD79b Wild-type | PFS by CD79b Status | 52 Days |
| CD79b Status Missing | PFS by CD79b Status | 56 Days |
Secondary
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.
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
Population: Full analysis set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | PFS by DLBCL/COO Subtype | 73 Days |
| CD79b Wild-type | PFS by DLBCL/COO Subtype | 52 Days |
| CD79b Status Missing | PFS by DLBCL/COO Subtype | 84 Days |
| DLBCL/COO Subtype Missing | PFS by DLBCL/COO Subtype | 51 Days |
Secondary
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.
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
Population: Full analysis set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | Progression-free Survival (PFS) in Total Population | 54 Days |
Other Pre-specified
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.
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)
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | ORR by CD79b Status Based on Central Imaging Review | 44.4 Percentage of participants |
| CD79b Wild-type | ORR by CD79b Status Based on Central Imaging Review | 20.0 Percentage of participants |
| CD79b Status Missing | ORR by CD79b Status Based on Central Imaging Review | 15.4 Percentage of participants |
Other Pre-specified
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.
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)
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | ORR by DLBCL/COO Subtype Based on Central Imaging Review | 47.4 Percentage of participants |
| CD79b Wild-type | ORR by DLBCL/COO Subtype Based on Central Imaging Review | 13.3 Percentage of participants |
| CD79b Status Missing | ORR by DLBCL/COO Subtype Based on Central Imaging Review | 0.0 Percentage of participants |
| DLBCL/COO Subtype Missing | ORR by DLBCL/COO Subtype Based on Central Imaging Review | 13.3 Percentage of participants |
Other Pre-specified
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.
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)
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | ORR in Total Population Based on Central Imaging Review | 22.4 Percentage of participants |
Other Pre-specified
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.
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
Population: Responders (i.e. participants with a best response of CR or PR) in full analysis set based on the investigator assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Copanlisib (Aliqopa, BAY80-6946) | Time to Response (TTR) in Total Population | 52 Days |