Lymphoma, Non-Hodgkin
Conditions
Keywords
Clinical trial, Phase III, Phosphatidylinositol-3-kinase, Non-Hodgkin's lymphoma, Indolent B-cell non-Hodgkin's lymphoma
Brief summary
The purpose of this study is to assess whether copanlisib in combination with standard immunochemotherapy (rituximab in combination with bendamustine \[R-B\] and rituximab in combination with a 4 drug combination of cyclophosphamide, doxorubicin, vincristine and prednisone/prednisolone \[R-CHOP\]) is effective and safe, compared with placebo in combination with standard immunochemotherapy (R-B or R-CHOP) in patients with relapsed iNHL who have received at least one, but at most three, lines of treatment, including rituximab-based immunochemotherapy and alkylating agents.
Detailed description
Patients should be in need of and fit for immunochemotherapy and should not be resistant to rituximab (resistance defined as lack of response or progression within 6 months of the last date of rituximab administration, including rituximab, and/or rituximab biosimilars, and/or anti-CD20 monoclonal antibody). This study will be composed of two parts: Safety run-in and phase III part. The purpose of the safety run-in part of this study is to assess whether the drug being tested (copanlisib) in combination with standard immunochemotherapy (R-B or R-CHOP) is safe and at what dose level of the study drug (copanlisib - 45mg or 60 mg) patients are able to tolerate the study treatment combination. In addition to finding a safe and tolerable dose level for the phase III part of the study, efficacy will also be evaluated for patients that stay on the study treatment during the safety run-in. The phase III part of the study started with the determined recommended dose of copanlisib of 60 mg in combination with R-B. Combination treatment of copanlisib at the recommended/approved dose of 60 mg with R-B or R-CHOP was completed in April 2021. A maximum of 24 patients will take part in the safety run-in part of this study. In the phase III part approximately 520 patients will be randomly assigned to blinded treatment arms of copanlisib plus R-B or R-CHOP or placebo plus R-B or R-CHOP. Combination therapy (copanlisib/placebo with R-B or R-CHOP) will be administered for a maximum of 6 cycles (C1-C6). Copanlisib/placebo (study drug) monotherapy will be administered from C7 onwards.
Interventions
Copanlisib is supplied as lyophilized preparation in a 6 mL injection vial. The total amount of copanlisib per vial is 60 mg. The solution for IV infusions is obtained after reconstitution with normal saline solution. For patients on R-B dosing of copanlisib will be administered on Days 1, 8 and 15 of each 28-day cycle. Copanlisib will be administered and then rituximab followed by bendamustine. For patients on R-CHOP dosing of copanlisib will be administered on Days 1 and 8 of each 21-day cycle. Treatment with copanlisib/placebo will be continued up to 12 months. Copanlisib will be administered before rituximab followed by cyclophosphamide, doxorubicin and vincristine infusions. Prednisone/prednisolone tablets to be taken for 5 days.
DRUGPlacebo
Placebo is supplied as lyophilized preparation in a 6 mL injection vial. The developed placebo lyophilisate is equivalent to the 60 mg copanlisib formulation, with regard to the composition of excipients and the instructions for reconstitution and dose preparation. Placebo dosing will be administered as per copanlisib described above. Applies to the phase III part of the study only.
DRUGRituximab
Rituximab is administered as an infusion at a dose of 375 mg/m2 body surface on Day 1 of each 28-day cycle for patients assigned to R-B and on Day 2 of each 21-day cycle for patients assigned to R-CHOP.
DRUGCyclophosphamide
Cyclophosphamide is administered as an infusion at a dose of 750 mg/m2 body surface on Day 2 of each 21-day cycle for patients assigned to R-CHOP
DRUGDoxorubicin
Doxorubicin is administered as an infusion at a dose of 50 mg/m2 body surface on Day 2 of each 21-day cycle for patients assigned to R-CHOP
DRUGVincristine
Vincristine is administered as an infusion at a dose of 1.4 mg/m2 body surface (maximum dose 2.0 mg) on Day 2 of each 21-day cycle for patients assigned to R-CHOP
DRUGBendamustine
Bendamustine is administered as an infusion at a dose of 90 mg/m2 body surface on Day 1 and Day 2 for patients assigned to R-B
DRUGPrednisone
Prednisone is given as 100 mg tablets daily from Day 2 to Day 6 for patients assigned to R-CHOP
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of B lymphocyte antigen CD20 positive iNHL with histological subtype limited to: * Follicular lymphoma G1-2-3a * Small lymphocytic lymphoma with absolute lymphocyte count \<5x10E9/L at study entry * Lymphoplasmacytoid lymphoma / Waldenström macroglobulinemia (LPL / WM) * Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal) * Patients must have relapsed (recurrence after complete response or presented progression after partial response) or progressed after at least one but at most three prior lines of therapy, including rituximab, and/or rituximab biosimilars, and/or anti-CD20 monoclonal antibody (e.g. obinutuzumab) -based immunochemotherapy and alkylating agents (if given concomitantly is considered one line of therapy). A previous regimen is defined as one of the following: at least 2 months of single-agent therapy (less than 2 months of therapy with single agent rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody can be considered a previous regimen in the case the patient responded to it); at least 2 consecutive cycles of polychemotherapy; autologous transplant; or radioimmunotherapy. Previous exposure to other PI3K Inhibitors (except copanlisib) is acceptable provided there is no resistance (resistance defined as no response (response defined as partial response \[PR\] or complete response \[CR\]) at any time during therapy, or progressive disease (PD) after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor. * Non-WM patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the Lugano Classification. For patients with splenic MZL this requirement may be restricted to splenomegaly alone since that is usually the only manifestation of measurable disease. * Patients affected by WM who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment must have measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level ≥ 2 x upper limit of normal and positive immunofixation test. * Male or female patients ≥ 18 years of age * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Life expectancy of at least 3 months * Availability of fresh tumor tissue and/or archival tumor tissue at Screening * Adequate baseline laboratory values as assessed within 7 days before starting study treatment. * Left ventricular ejection fraction ≥ 50%
Exclusion criteria
* Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease, or chronic lymphocytic leukemia. In patients with clinical suspicion of transformed disease, a fresh biopsy is recommended. * Rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody (e.g. obinutuzumab) resistance at any line of therapy (resistance defined as lack of response, or progression within 6 months of the last date of rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody administration, including maintenance with these drugs). * HbA1c \> 8.5% at screening * History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator) * Known lymphomatous involvement of the central nervous system * Known history of human immunodeficiency virus (HIV) infection * Hepatitis B (HBV) or hepatitis C (HCV) infection. Patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy as per rituximab label. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA. * Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible.CMV PCR test is considered positive if, the result can be interpreted as a CMV viremia according to local standard of care. * Uncontrolled hypertension despite optimal medical management (per investigator´s assessment) * Congestive heart failure \> New York Heart Association (NYHA) class 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SRI: Occurrence of Dose-limiting Toxicities (DLT) | At Cycle 1: 28 days for Copa+R-B or 21 days for Copa+R-CHOP | Dose-limiting toxicity is defined as any of the following occurring during Cycle 1 at a given dose level and regarded by the investigator and/or the sponsor to be possibly, probably, or definitely related to copanlisib given in combination with R-B or R-CHOP. General: any grade 5 hematologic or non-hematologic toxicity or any delay of \>2 weeks of Cycle 2 due to study treatment-related toxicity; Non-hematologic DLT: any non-hematologic toxicity grade ≥ 3; Hematologic DLT: grade 4 absolute neutrophil count decrease lasting \>7 days, or grade 4 febrile neutropenia, or grade 4 platelet count decreased or grade 3 platelet count decreased with serious bleeding, or signs of serious bleeding and/or international normalized ratio (INR) increased or partial thromboplastin time (PTT) prolonged of grade 3. |
| Phase 3: Progression-free Survival (PFS) by Independent Central Review | Approximately 6 years 4 months | PFS is defined as the time from randomization to progressive disease (PD) or death from any cause (if no progression is documented). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 3: Objective Tumor Response Rate (ORR)-Independent Central Review | Up to 6 years 4 months | ORR, as assessed by independent central review, is defined as the percentage of participants who had a best response rating of CR or PR according to the Lugano classification and for subjects with LPL/WM, a response rating of CR, VGPR, PR, or MR according to the Owen criteria, over the whole duration of the study (i.e., until time of analysis of PFS). |
| Phase 3: ORR-Investigator Assessment | Up to 6 years 4 months | ORR, as assessed by investigator, is defined as the percentage of participants who had a best response rating of CR or PR according to the Lugano classification and for subjects with LPL/WM, a response rating of CR, VGPR, PR, or MR according to the Owen criteria, over the whole duration of the study (i.e., until time of analysis of PFS). |
| Phase 3: Duration of Tumor Response (DOR)-Independent Central Review | Approximately 6 years 4 months | DOR, as assessed by independent central review, is defined as the time (in days) from first observed tumor response (CR, VGPR, PR, or MR) until progression or death from any cause, whichever occurred earlier. The DOR was only defined for patients with at least 1 CR, VGPR, PR, or MR. |
| Phase 3: DOR-Investigator Assessment | Approximately 6 years 4 months | DOR, as assessed by investigator, is defined as the time (in days) from first observed tumor response (CR, VGPR, PR, or MR) until progression or death from any cause, whichever occurred earlier. The DOR was only defined for patients with at least 1 CR, VGPR, PR, or MR. |
| Phase 3: Complete Tumor Response Rate (CRR)-Independent Central Review | Approximately 6 years 4 months | CRR, as assessed by independent central review, is defined as the proportion of patients who had a best response rating of CR according to the Lugano classification, and for patients with LPL/WM, a response rating of CR according to the Owen criteria, over the whole duration of the study (i.e., until the time of analysis of PFS). |
| Phase 3: CRR-Investigator Assessment | Approximately 6 years 4 months | CRR, as assessed by investigator, is defined as the proportion of patients who had a best response rating of CR according to the Lugano classification, and for patients with LPL/WM, a response rating of CR according to the Owen criteria, over the whole duration of the study (i.e., until the time of analysis of PFS). |
| Phase 3: Disease Control Rate (DCR)-Independent Central Review | Approximately 6 years 4 months | DCR, as assessed by independent central review, is defined as the proportion of patients who had a best response rating of CR, VGPR, PR, MR, or stable disease (excluding unconfirmed early stable disease). |
| SRI: Best Overall Response | Approximately 7 years 8 months | Best overall response is defined as the best response achieved during the treatment and active follow-up periods; prior to end of study or start of new anti-tumor treatment, whichever occurs first. |
| Phase 3: Time to Tumor Progression (TTP)-Independent Central Review | Approximately 6 years 4 months | TTP, as assessed by independent central review, is defined as the time from randomization to progression or death related to progression, whichever occurred earlier. Death related to progression was any death except for: death due to an AE unrelated to progression; or death with a specification of other as reason (which excludes PD). |
| Phase 3: TTP-Investigator Assessment | Approximately 6 years 4 months | TTP, as assessed by investigator, is defined as the time from randomization to progression or death related to progression, whichever occurred earlier. Death related to progression was any death except for: death due to an AE unrelated to progression; or death with a specification of other as reason (which excludes PD). |
| Phase 3: Time to Next Anti-lymphoma Treatment (TTNT) | Approximately 6 years 4 months | A new anti-lymphoma therapy is any new systemic anticancer treatment or radiotherapy for lymphoma, with a consolidation intent. TTNT was defined as the time from the date of randomization to the start of new anti-lymphoma therapy, where the date of randomization was considered Day 1. |
| Phase 3: Overall Survival (OS) | Approximately 6 years 4 months | Overall survival is defined as the time from randomization until death from any cause. The OS for patients alive at the time of the database cut-off date was censored to the last date they were known to be alive. Deaths that occurred after the database cut-off date, reported during data cleaning, were considered for establishing the last known alive date at data cut-off. |
| Phase 3: Time to Deterioration in Disease-related Symptoms-physical (DRS-P) of at Least 3 Points of Lymphoma | Approximately 6 years 4 months | Time to deterioration in DRS-P of at least 3 points, as measured by the FLymSI-18 questionnaire, was evaluated in all patients. It is defined as the time from randomization to DRS-P decline, progression, or death from any reason, whichever occurred earlier. |
| Phase 3: Time to Improvement in Disease-related Symptoms-physical (DRS-P) of at Least 3 Points of Lymphoma | Approximately 6 years 4 months | Time to improvement in DRS-P of at least 3 points, as measured by the FLymSI-18 questionnaire, was evaluated for all patients. It is defined as the time from randomization to DRS-P improvement of at least 3 points. |
| Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Approximately 4 years | A treatment-emergent AE is defined as any event arising or worsening after start of study drug administration until 30 days after the last study drug intake. |
| Phase 3: DCR-Investigator Assessment | Approximately 6 years 4 months | DCR, as assessed by investigator, is defined as the proportion of patients who had a best response rating of CR, VGPR, PR, MR, or stable disease (excluding unconfirmed early stable disease). |
| SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Approximately 4 years 10 months | A treatment-emergent AE is defined as any event arising or worsening after start of study drug administration until 30 days after the last study drug intake. |
Countries
Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Mexico, Poland, Portugal, Romania, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
SRI part screened 42 participants from 12 countries, between 06-Jan-2016 (first participants first visit \[FPFV\]) and 31-Oct-2019 (last participant first visit \[LPFV\]). Phase 3 part screened 672 participants from 35 countries/regions, between 06-Feb-2017 (FPFV) and 31-Mar-2020(LPFV). Study terminated on 10-Nov-2023,
Pre-assignment details
SRI: 42 participants were screened, 15 participants discontinued screening, 27 participants were enrolled and administered treatment. Phase 3: 672 participants were screened, 148 discontinued screening. 524 participants were enrolled and randomized to treatment. 4 participants were randomized but never administered, 520 participants were randomized and administered treatment.
Participants by arm
| Arm | Count |
|---|---|
| SRI: Copa+R-B 45 mg In SRI part, participants received copanlisib at dose level of 45 mg in combination with R-B. | 3 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) In SRI part, participants received copanlisib at dose level of 60 mg in combination with R-B. | 7 |
| SRI: Copa+R-CHOP 45 mg In SRI part, participants received copanlisib at dose level of 45 mg in combination with R-CHOP. | 5 |
| SRI: Copa+R-CHOP 60 mg In SRI part, participants received copanlisib at dose level of 60 mg in combination with R-CHOP. | 6 |
| SRI: Japan Copa+R-B 60 mg In SRI part, participants from Japan received copanlisib at dose level of 60 mg in combination with R-B. | 6 |
| Phase 3: Copa+R-B/R-CHOP In Phase 3 part, participants who never received R-B as a previous line of therapy were randomized to copanlisib + R-B. Participants who received R-B as a previous line of therapy were randomized to copanlisib + R-CHOP or, if progression-free interval after the last R-B treatment was ≥ 24 months, to copanlisib + R-B. | 262 |
| Phase 3: Pbo+R-B/R-CHOP In Phase 3 part, participants who never received R-B as a previous line of therapy were randomized to placebo + R-B. Participants who received R-B as a previous line of therapy were randomized to placebo + R-CHOP or, if progression-free interval after the last R-B treatment was ≥ 24 months, to placebo + R-B. | 262 |
| Total | 551 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | AE associated with clinical disease progression | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| Overall Study | AE not associated with clinical disease progression | 1 | 1 | 0 | 2 | 1 | 65 | 21 |
| Overall Study | Logistical reason: COVID-19 pandemic related | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 1 | 1 | 0 | 0 | 0 | 17 | 23 |
| Overall Study | Patient decision | 0 | 1 | 0 | 0 | 1 | 36 | 22 |
| Overall Study | Patient decision: COVID-19 pandemic related | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 2 | 2 | 2 | 1 | 10 | 3 |
| Overall Study | Physician decision: COVID-19 pandemic related | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Progressive disease - clinical progression | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| Overall Study | Progressive disease - radiological progression | 0 | 0 | 0 | 0 | 0 | 11 | 22 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Study intervention never administered | 0 | 0 | 0 | 0 | 0 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 10 | 6 |
Baseline characteristics
| Characteristic | Total | SRI: Copa+R-B 45 mg | SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Copa+R-CHOP 45 mg | SRI: Copa+R-CHOP 60 mg | SRI: Japan Copa+R-B 60 mg | Phase 3: Copa+R-B/R-CHOP | Phase 3: Pbo+R-B/R-CHOP |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 211 Participants | 1 Participants | 3 Participants | 1 Participants | 4 Participants | 0 Participants | 102 Participants | 100 Participants |
| Age, Categorical Between 18 and 65 years | 340 Participants | 2 Participants | 4 Participants | 4 Participants | 2 Participants | 6 Participants | 160 Participants | 162 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 56 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 24 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 464 Participants | 3 Participants | 7 Participants | 5 Participants | 5 Participants | 6 Participants | 223 Participants | 215 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 31 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 15 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 189 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 6 Participants | 98 Participants | 82 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 26 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 15 Participants | 10 Participants |
| Race (NIH/OMB) White | 328 Participants | 2 Participants | 5 Participants | 3 Participants | 6 Participants | 0 Participants | 144 Participants | 168 Participants |
| Sex: Female, Male Female | 246 Participants | 3 Participants | 5 Participants | 4 Participants | 1 Participants | 2 Participants | 103 Participants | 128 Participants |
| Sex: Female, Male Male | 305 Participants | 0 Participants | 2 Participants | 1 Participants | 5 Participants | 4 Participants | 159 Participants | 134 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 0 / 7 | 0 / 5 | 1 / 6 | 0 / 6 | 68 / 263 | 62 / 257 |
| other Total, other adverse events | 3 / 3 | 7 / 7 | 5 / 5 | 6 / 6 | 6 / 6 | 259 / 263 | 250 / 257 |
| serious Total, serious adverse events | 2 / 3 | 3 / 7 | 3 / 5 | 6 / 6 | 3 / 6 | 161 / 263 | 54 / 257 |
Outcome results
Primary
Phase 3: Progression-free Survival (PFS) by Independent Central Review
PFS is defined as the time from randomization to progressive disease (PD) or death from any cause (if no progression is documented).
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Progression-free Survival (PFS) by Independent Central Review | 32.9 Months |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Progression-free Survival (PFS) by Independent Central Review | 33.3 Months |
p-value: =0.82797495% CI: [0.881, 1.437]Log Rank
Primary
SRI: Occurrence of Dose-limiting Toxicities (DLT)
Dose-limiting toxicity is defined as any of the following occurring during Cycle 1 at a given dose level and regarded by the investigator and/or the sponsor to be possibly, probably, or definitely related to copanlisib given in combination with R-B or R-CHOP. General: any grade 5 hematologic or non-hematologic toxicity or any delay of \>2 weeks of Cycle 2 due to study treatment-related toxicity; Non-hematologic DLT: any non-hematologic toxicity grade ≥ 3; Hematologic DLT: grade 4 absolute neutrophil count decrease lasting \>7 days, or grade 4 febrile neutropenia, or grade 4 platelet count decreased or grade 3 platelet count decreased with serious bleeding, or signs of serious bleeding and/or international normalized ratio (INR) increased or partial thromboplastin time (PTT) prolonged of grade 3.
Time frame: At Cycle 1: 28 days for Copa+R-B or 21 days for Copa+R-CHOP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SRI: Copa+R-B 45 mg | SRI: Occurrence of Dose-limiting Toxicities (DLT) | 0 Percentage |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Occurrence of Dose-limiting Toxicities (DLT) | 0 Percentage |
| SRI: Copa+R-CHOP 45 mg | SRI: Occurrence of Dose-limiting Toxicities (DLT) | 0 Percentage |
| SRI: Copa+R-CHOP 60 mg | SRI: Occurrence of Dose-limiting Toxicities (DLT) | 0 Percentage |
| SRI: Japan Copa+R-B 60 mg | SRI: Occurrence of Dose-limiting Toxicities (DLT) | 16.7 Percentage |
Secondary
Phase 3: Complete Tumor Response Rate (CRR)-Independent Central Review
CRR, as assessed by independent central review, is defined as the proportion of patients who had a best response rating of CR according to the Lugano classification, and for patients with LPL/WM, a response rating of CR according to the Owen criteria, over the whole duration of the study (i.e., until the time of analysis of PFS).
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Complete Tumor Response Rate (CRR)-Independent Central Review | 38.5 Percentage | 95% Confidence Interval 32.6 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Complete Tumor Response Rate (CRR)-Independent Central Review | 41.2 Percentage | 95% Confidence Interval 35.2 |
p-value: =0.74115395% CI: [-11.06, 5.57]Cochran-Mantel-Haenszel
Secondary
Phase 3: CRR-Investigator Assessment
CRR, as assessed by investigator, is defined as the proportion of patients who had a best response rating of CR according to the Lugano classification, and for patients with LPL/WM, a response rating of CR according to the Owen criteria, over the whole duration of the study (i.e., until the time of analysis of PFS).
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: CRR-Investigator Assessment | 39.7 Percentage |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: CRR-Investigator Assessment | 42.0 Percentage |
p-value: =0.69648295% CI: [-10.62, 6.2]Cochran-Mantel-Haenszel
Secondary
Phase 3: DCR-Investigator Assessment
DCR, as assessed by investigator, is defined as the proportion of patients who had a best response rating of CR, VGPR, PR, MR, or stable disease (excluding unconfirmed early stable disease).
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: DCR-Investigator Assessment | 88.5 Percentage | 95% Confidence Interval 84.1 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: DCR-Investigator Assessment | 92.4 Percentage | 95% Confidence Interval 88.5 |
p-value: =0.94424295% CI: [-8.68, 0.9]Cochran-Mantel-Haenszel
Secondary
Phase 3: Disease Control Rate (DCR)-Independent Central Review
DCR, as assessed by independent central review, is defined as the proportion of patients who had a best response rating of CR, VGPR, PR, MR, or stable disease (excluding unconfirmed early stable disease).
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Disease Control Rate (DCR)-Independent Central Review | 88.5 Percentage | 95% Confidence Interval 84.1 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Disease Control Rate (DCR)-Independent Central Review | 92.4 Percentage | 95% Confidence Interval 88.5 |
p-value: =0.93600995% CI: [-9.04, 1.14]Cochran-Mantel-Haenszel
Secondary
Phase 3: DOR-Investigator Assessment
DOR, as assessed by investigator, is defined as the time (in days) from first observed tumor response (CR, VGPR, PR, or MR) until progression or death from any cause, whichever occurred earlier. The DOR was only defined for patients with at least 1 CR, VGPR, PR, or MR.
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: DOR-Investigator Assessment | 32.4 Months |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: DOR-Investigator Assessment | 30.9 Months |
p-value: =0.80173595% CI: [0.865, 1.443]Log Rank
Secondary
Phase 3: Duration of Tumor Response (DOR)-Independent Central Review
DOR, as assessed by independent central review, is defined as the time (in days) from first observed tumor response (CR, VGPR, PR, or MR) until progression or death from any cause, whichever occurred earlier. The DOR was only defined for patients with at least 1 CR, VGPR, PR, or MR.
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Duration of Tumor Response (DOR)-Independent Central Review | 32.2 Months | 95% Confidence Interval 22.8 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Duration of Tumor Response (DOR)-Independent Central Review | 32.4 Months | 95% Confidence Interval 27.7 |
p-value: =0.84620495% CI: [0.883, 1.484]Log Rank
Secondary
Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE)
A treatment-emergent AE is defined as any event arising or worsening after start of study drug administration until 30 days after the last study drug intake.
Time frame: Approximately 4 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any TEAE | 263 Participants |
| SRI: Copa+R-B 45 mg | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | TESAEs | 161 Participants |
| SRI: Copa+R-B 45 mg | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any copanlisib or placebo related TEAE | 250 Participants |
| SRI: Copa+R-B 45 mg | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any copanlisib or placebo related TESAEs | 118 Participants |
| SRI: Copa+R-B 45 mg | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any R-B/R-CHOP related TEAE | 245 Participants |
| SRI: Copa+R-B 45 mg | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any R-B/R-CHOP related TESAEs | 109 Participants |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any copanlisib or placebo related TESAEs | 26 Participants |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any TEAE | 250 Participants |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any R-B/R-CHOP related TESAEs | 26 Participants |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | TESAEs | 54 Participants |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any R-B/R-CHOP related TEAE | 224 Participants |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any copanlisib or placebo related TEAE | 214 Participants |
Secondary
Phase 3: Objective Tumor Response Rate (ORR)-Independent Central Review
ORR, as assessed by independent central review, is defined as the percentage of participants who had a best response rating of CR or PR according to the Lugano classification and for subjects with LPL/WM, a response rating of CR, VGPR, PR, or MR according to the Owen criteria, over the whole duration of the study (i.e., until time of analysis of PFS).
Time frame: Up to 6 years 4 months
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Objective Tumor Response Rate (ORR)-Independent Central Review | 85.5 Percentage | 95% Confidence Interval 80.6 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Objective Tumor Response Rate (ORR)-Independent Central Review | 86.6 Percentage | 95% Confidence Interval 81.9 |
p-value: =0.65865295% CI: [-7.25, 4.75]Cochran-Mantel-Haenszel
Secondary
Phase 3: ORR-Investigator Assessment
ORR, as assessed by investigator, is defined as the percentage of participants who had a best response rating of CR or PR according to the Lugano classification and for subjects with LPL/WM, a response rating of CR, VGPR, PR, or MR according to the Owen criteria, over the whole duration of the study (i.e., until time of analysis of PFS).
Time frame: Up to 6 years 4 months
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: ORR-Investigator Assessment | 85.5 Percentage | 95% Confidence Interval 80.6 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: ORR-Investigator Assessment | 86.6 Percentage | 95% Confidence Interval 81.9 |
p-value: =0.60518395% CI: [-6.64, 5.05]Cochran-Mantel-Haenszel
Secondary
Phase 3: Overall Survival (OS)
Overall survival is defined as the time from randomization until death from any cause. The OS for patients alive at the time of the database cut-off date was censored to the last date they were known to be alive. Deaths that occurred after the database cut-off date, reported during data cleaning, were considered for establishing the last known alive date at data cut-off.
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Overall Survival (OS) | NA Months |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Overall Survival (OS) | NA Months |
p-value: =0.75856395% CI: [0.8, 1.603]Log Rank
Secondary
Phase 3: Time to Deterioration in Disease-related Symptoms-physical (DRS-P) of at Least 3 Points of Lymphoma
Time to deterioration in DRS-P of at least 3 points, as measured by the FLymSI-18 questionnaire, was evaluated in all patients. It is defined as the time from randomization to DRS-P decline, progression, or death from any reason, whichever occurred earlier.
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Time to Deterioration in Disease-related Symptoms-physical (DRS-P) of at Least 3 Points of Lymphoma | 2.7 Months | 95% Confidence Interval 1.9 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Time to Deterioration in Disease-related Symptoms-physical (DRS-P) of at Least 3 Points of Lymphoma | 6.3 Months | 95% Confidence Interval 4.6 |
p-value: =0.99969595% CI: [1.149, 1.691]Log Rank
Secondary
Phase 3: Time to Improvement in Disease-related Symptoms-physical (DRS-P) of at Least 3 Points of Lymphoma
Time to improvement in DRS-P of at least 3 points, as measured by the FLymSI-18 questionnaire, was evaluated for all patients. It is defined as the time from randomization to DRS-P improvement of at least 3 points.
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Time to Improvement in Disease-related Symptoms-physical (DRS-P) of at Least 3 Points of Lymphoma | 12.8 Months | 95% Confidence Interval 6.7 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Time to Improvement in Disease-related Symptoms-physical (DRS-P) of at Least 3 Points of Lymphoma | 5.1 Months | 95% Confidence Interval 2.8 |
p-value: =0.96563995% CI: [0.642, 1.02]Log Rank
Secondary
Phase 3: Time to Next Anti-lymphoma Treatment (TTNT)
A new anti-lymphoma therapy is any new systemic anticancer treatment or radiotherapy for lymphoma, with a consolidation intent. TTNT was defined as the time from the date of randomization to the start of new anti-lymphoma therapy, where the date of randomization was considered Day 1.
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Time to Next Anti-lymphoma Treatment (TTNT) | NA Months |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Time to Next Anti-lymphoma Treatment (TTNT) | NA Months |
p-value: =0.95586595% CI: [0.962, 1.728]Log Rank
Secondary
Phase 3: Time to Tumor Progression (TTP)-Independent Central Review
TTP, as assessed by independent central review, is defined as the time from randomization to progression or death related to progression, whichever occurred earlier. Death related to progression was any death except for: death due to an AE unrelated to progression; or death with a specification of other as reason (which excludes PD).
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: Time to Tumor Progression (TTP)-Independent Central Review | 36.1 Months | 95% Confidence Interval 30.3 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: Time to Tumor Progression (TTP)-Independent Central Review | 35.0 Months | 95% Confidence Interval 30.4 |
p-value: =0.51784995% CI: [0.777, 1.303]Log Rank
Secondary
Phase 3: TTP-Investigator Assessment
TTP, as assessed by investigator, is defined as the time from randomization to progression or death related to progression, whichever occurred earlier. Death related to progression was any death except for: death due to an AE unrelated to progression; or death with a specification of other as reason (which excludes PD).
Time frame: Approximately 6 years 4 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | Phase 3: TTP-Investigator Assessment | 36.1 Months | 95% Confidence Interval 30.3 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | Phase 3: TTP-Investigator Assessment | 35.0 Months | 95% Confidence Interval 30.4 |
p-value: =0.41139895% CI: [0.75, 1.257]Log Rank
Secondary
SRI: Best Overall Response
Best overall response is defined as the best response achieved during the treatment and active follow-up periods; prior to end of study or start of new anti-tumor treatment, whichever occurs first.
Time frame: Approximately 7 years 8 months
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | BR - Unconfirmed early stable disease (uSD) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | Best response (BR) -Complete response (CR) | 33.3 Percentage | 95% Confidence Interval 0.8 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | Response rate - Disease control rate (DCR) | 100.0 Percentage | 95% Confidence Interval 29.2 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | BR - Very good partial response (VGPR) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | BR - Not evaluable | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | BR - Minor response (MR) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | Response rate - Objective response rate (ORR) | 100.0 Percentage | 95% Confidence Interval 29.2 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | BR - Progressive disease (PD) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | BR - Stable disease | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | BR - Partial response (PR) | 66.7 Percentage | 95% Confidence Interval 9.4 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | Response rate - Complete response rate (CRR) | 33.3 Percentage | 95% Confidence Interval 0.8 |
| SRI: Copa+R-B 45 mg | SRI: Best Overall Response | BR - Not available | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | BR - Partial response (PR) | 28.6 Percentage | 95% Confidence Interval 3.7 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | BR - Progressive disease (PD) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | BR - Unconfirmed early stable disease (uSD) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | BR - Very good partial response (VGPR) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | Best response (BR) -Complete response (CR) | 71.4 Percentage | 95% Confidence Interval 29 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | Response rate - Disease control rate (DCR) | 100.0 Percentage | 95% Confidence Interval 59 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | BR - Not evaluable | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | Response rate - Objective response rate (ORR) | 100.0 Percentage | 95% Confidence Interval 59 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | BR - Minor response (MR) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | Response rate - Complete response rate (CRR) | 71.4 Percentage | 95% Confidence Interval 29 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | BR - Not available | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Best Overall Response | BR - Stable disease | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | Response rate - Disease control rate (DCR) | 100.0 Percentage | 95% Confidence Interval 47.8 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | Best response (BR) -Complete response (CR) | 60.0 Percentage | 95% Confidence Interval 14.7 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | BR - Very good partial response (VGPR) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | BR - Partial response (PR) | 20.0 Percentage | 95% Confidence Interval 0.5 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | BR - Minor response (MR) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | BR - Stable disease | 20.0 Percentage | 95% Confidence Interval 0.5 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | BR - Progressive disease (PD) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | BR - Unconfirmed early stable disease (uSD) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | BR - Not evaluable | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | BR - Not available | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | Response rate - Objective response rate (ORR) | 80.0 Percentage | 95% Confidence Interval 28.4 |
| SRI: Copa+R-CHOP 45 mg | SRI: Best Overall Response | Response rate - Complete response rate (CRR) | 60.0 Percentage | 95% Confidence Interval 14.7 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | BR - Progressive disease (PD) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | Best response (BR) -Complete response (CR) | 16.7 Percentage | 95% Confidence Interval 0.4 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | BR - Not evaluable | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | BR - Stable disease | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | BR - Not available | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | BR - Minor response (MR) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | Response rate - Complete response rate (CRR) | 16.7 Percentage | 95% Confidence Interval 0.4 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | Response rate - Objective response rate (ORR) | 100.0 Percentage | 95% Confidence Interval 54.1 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | BR - Partial response (PR) | 83.3 Percentage | 95% Confidence Interval 35.9 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | BR - Very good partial response (VGPR) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | Response rate - Disease control rate (DCR) | 100.0 Percentage | 95% Confidence Interval 54.1 |
| SRI: Copa+R-CHOP 60 mg | SRI: Best Overall Response | BR - Unconfirmed early stable disease (uSD) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | BR - Progressive disease (PD) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | Response rate - Objective response rate (ORR) | 83.3 Percentage | 95% Confidence Interval 35.9 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | Best response (BR) -Complete response (CR) | 50.0 Percentage | 95% Confidence Interval 11.8 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | BR - Not evaluable | 16.7 Percentage | 95% Confidence Interval 0.4 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | BR - Very good partial response (VGPR) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | BR - Minor response (MR) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | Response rate - Complete response rate (CRR) | 50.0 Percentage | 95% Confidence Interval 11.8 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | BR - Stable disease | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | BR - Not available | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | BR - Unconfirmed early stable disease (uSD) | 0 Percentage | 95% Confidence Interval 0 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | BR - Partial response (PR) | 33.3 Percentage | 95% Confidence Interval 4.3 |
| SRI: Japan Copa+R-B 60 mg | SRI: Best Overall Response | Response rate - Disease control rate (DCR) | 83.3 Percentage | 95% Confidence Interval 35.9 |
Secondary
SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE)
A treatment-emergent AE is defined as any event arising or worsening after start of study drug administration until 30 days after the last study drug intake.
Time frame: Approximately 4 years 10 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SRI: Copa+R-B 45 mg | SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any TEAE | 3 Participants |
| SRI: Copa+R-B 45 mg | SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | TESAEs | 2 Participants |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any TEAE | 7 Participants |
| SRI: Copa+R-B 60 mg (Excluding Subjects From Japan) | SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | TESAEs | 3 Participants |
| SRI: Copa+R-CHOP 45 mg | SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any TEAE | 5 Participants |
| SRI: Copa+R-CHOP 45 mg | SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | TESAEs | 3 Participants |
| SRI: Copa+R-CHOP 60 mg | SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | TESAEs | 6 Participants |
| SRI: Copa+R-CHOP 60 mg | SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any TEAE | 6 Participants |
| SRI: Japan Copa+R-B 60 mg | SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | Any TEAE | 6 Participants |
| SRI: Japan Copa+R-B 60 mg | SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE) | TESAEs | 3 Participants |