Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma
Conditions
Keywords
Lymphoma, Chronic Lymphocytic Leukemia, Durvalumab, Anti-PD-L1 Antibody, MEDI4736, Immune Checkpoint, Lymphatic Disease, B-Cell Malignancies, Abscopal Effect, Lenalidomide, Bendamustine, Rituximab, Ibrutinib, Lymphoma, B-Cell, Lymphoma, Non Hodgkin,, Hodgkin Disease, Leukemia, Lymphocytic, Chronic, B-Cell,, Lymphoma, Follicular, Lymphoma, Diffuse Large B-Cell, Lymphoma, Mantle Cell, Lymphoma, Small Lymphocytic, Immune System Diseases, Immunoproliferative Disorders, Lymphoproliferative Disorders
Brief summary
This study is designed to determine the recommended phase 2 dose (RP2D), and the safety, and efficacy of durvalumab as monotherapy and when given in combination with lenalidomide and rituximab; ibrutinib; or bendamustine and rituximab at the RP2D in adults with lymphoma or chronic lymphocytic leukemia (CLL).
Detailed description
The study was to consist of 3 parts: dose-finding, dose-confirmation, and dose-expansion. In this study, 4 treatment arms were to be investigated: * Arm A: durvalumab and lenalidomide ± rituximab * Arm B: durvalumab and ibrutinib * Arm C: durvalumab and rituximab ± bendamustine * Arm D: durvalumab (monotherapy) The study was to start with 3 dose-finding cohorts (Arms A, B, and C) and 1 dose-confirmation cohort (Arm D) in parallel. All treatment arms were to be open for enrollment at study start except in the US, where Arm D was to enroll depending on the availability of treatment slots and following the completion of assessment of responses from the combination therapy arms. For Arms A and C, prior to enrolling participants to receive all 3 drugs, the doublet combinations were to be evaluated. Once the doublet combinations were deemed tolerable, the eventual triplet combinations were to be tested. On 05 September 2017, the US FDA issued a Partial Clinical Hold on the study Arm A. Following this Partial Clinical Hold no more participants were enrolled into study Arm A. Participants already enrolled and treated in Arm A who were receiving clinical benefit, based on the discretion of the investigator, could continue study treatment after being reconsented. Arm B and C completed dose confirmation. The dose expansion part of the study was not opened.
Interventions
DRUGDurvalumab
Administered as an IV infusion (250 mL) over approximately 1 hour in duration
DRUGLenalidomide
Administered orally
DRUGRituximab
Administered by intravenous infusion
DRUGIbrutinib
Administered orally
DRUGBendamustine
Administered as a 30-minute intravenous infusion
Sponsors
Celgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Within Arms A, B, and C participants on the dose-finding part were enrolled sequentially according to a 3+3 design. All treatment arms were to be open for enrollment at study start except in the US, where Arm D was to enroll depending on the availability of treatment slots and following the completion of assessment of responses from the combination therapy arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject who has histologically confirmed and documented B-cell lymphoma (eg, follicular, diffuse large B-cell, mantle cell, small lymphocytic, or Hodgkin lymphoma) and chronic lymphocytic leukemia. 2. Subject who has high-risk chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). 3. Subject who was previously treated with at least one prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy. 4. Subject who has the Eastern Cooperative Oncology Group performance status of 0, 1, or 2. 5. Subject who is willing and able to undergo biopsy. 6. Subject who has documented active relapsed or refractory disease requiring therapeutic intervention. 7. Subject with lymphoma who has measurable disease (≥ 2.0 cm in its longest dimension by computed tomography) or chronic lymphocytic leukemia in need of treatment. 8. Subject who fulfills the laboratory requirements as per protocol
Exclusion criteria
1. Subject who has central nervous system (CNS) or meningeal involvement by lymphoma. 2. Subject who has any histopathologic finding consistent with myelodysplastic syndrome on bone marrow studies. 3. Subject who received any prior monoclonal antibodies against programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) and/or any prior: 1. Arm A only: drugs with immunomodulatory and other properties (eg, lenalidomide, thalidomide); 2. Arm B only: ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor; 3. Arms C only: bendamustine 4. Subject who has active auto-immune disease. 5. Subject who has history of organ transplant or allogeneic hematopoietic stem cell transplantation. 6. Subject who is seropositive for or active viral infection with hepatitis B virus (HBV) (hepatitis B surface antigen \[HBsAg\] positive and/or detectable viral DNA) 7. Subject who has known seropositivity for or active infection for human immunodeficiency virus (HIV) or hepatitis C virus (HCV). 8. Subject who has history of primary immunodeficiency or tuberculosis. 9. Subject who other invasive malignancy within 2 years (5 years for Arm A) except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin, ductal carcinoma in situ of the breast, or incidental histologic finding of prostate cancer (T1a or T1b using the TNM \[tumor, nodes, metastasis\] clinical staging system) that has/have been surgically cured.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Cycle 1 (28 days) | Dose limiting toxicities were evaluated during the DLT evaluation period for participants in the dose finding cohorts. The severity grading was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT is defined as below: Hematologic DLT • Grade 4 neutropenia observed for greater than 5 days duration • Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration • Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement for platelets transfusion • Grade 4 anemia, unexplained by underlying disease • Any other grade 4 hematologic toxicity that does not resolve to participant's pretreatment baseline level within 72 hours. Non-Hematologic DLT • Any non-hematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by medical management • Any treatment interruption greater than 2 weeks due to adverse event. |
| Number of Participants With Treatment-emergent Adverse Events | From first dose of any study drug to 90 days after last dose of durvalumab or 28 days after last dose of other study drugs, up to the data cut-off date of 6 March 2019. Maximum time on treatment was 55.4 weeks for DUR and 130 weeks for other study drugs. | Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) occurring or worsening on or after the first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. The intensity of AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by the investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Response | From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months. | Time to response was calculated as the time from first dose of study drug to the first response date (CR or PR for lymphoma participants and CR, CRi, nPR, PR, or PRL for CLL participants). |
| Kaplan-Meier Estimate of Duration of Response | From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months. | Duration of response is defined for responders only as the time from the first documented response (CR or PR for lymphoma participants or CR, CRi, nPR, PR, or PRL for CLL participants) to disease progression or death (from any cause). For participants with response but no progression, or death, duration of response was censored at the last date that the participant was known to be progression-free. |
| Kaplan-Meier Estimate of Progression-free Survival (PFS) | From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months. | Progression-free survival was calculated as the time from first dose of study drug to the first documented progression or death (from any cause) during the entire efficacy evaluation period. For participants with no progression or death, PFS was censored at the last assessment date the participant was known to be progression-free. |
| Maximum Observed Plasma Concentration (Cmax) of Durvalumab | Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion. | — |
| Time to Maximum Plasma Concentration (Tmax) of Durvalumab | Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion. | — |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab | Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion. | — |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab | Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion. | — |
| Terminal Elimination Phase Half-Life (t½) of Durvalumab | Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion. | — |
| Overall Response Rate (ORR) During Durvalumab Treatment | Up to 13 cycles (12 months) | For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percent of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL). |
| Volume of Distribution (Vz) of Durvalumab | Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion. | — |
| Maximum Observed Plasma Concentration (Cmax) of Lenalidomide | Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose. | — |
| Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide | Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose. | — |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide | Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose | — |
| Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose. | — |
| Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib | Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose. | — |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib | Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose | — |
| Change From Baseline in Soluble Programmed Cell Death Ligand-1 (sPD-L1) Concentration | Baseline (Cycle 1 Day 1 predose) and Day 1 of Cycles 2 to 13 | Change from baseline in sPD-L1 could not be calculated as all post-baseline samples were below the lower limit of quantification (\<15.60 pg/mL). |
| Clearance (CL) of Durvalumab | Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion. | — |
| Overall Response Rate During the Entire Study | From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months. | For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification) (Cheson, 2014). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percentage of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL). |
Countries
France, Germany, Italy, Japan, Netherlands, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg Participants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL. | 3 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab (RIT) 375 mg/m² IV infusion on Days 2, 8, 15, and 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5. | 3 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5. | 8 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib (IBR) 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason. | 3 |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason. | 4 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose). | 3 |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6. | 1 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose). | 4 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose). | 5 |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason. | 10 |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason. | 10 |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6. | 10 |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6. | 10 |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose). | 5 |
| Part 2, Arm D FL: DUR 1500 mg Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13. | 5 |
| Part 2, Arm D DLBCL: DUR 1500 mg Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13. | 10 |
| Part 2, Arm D CLL/SLL: DUR 1500 mg Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13. | 2 |
| Part 2, Arm D MCL: DUR 1500 mg Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13. | 5 |
| Part 2, Arm D HL: DUR 1500 mg Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13. | 5 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 2 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 |
| Overall Study | Other Reasons | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 2 | 1 | 3 | 1 | 2 | 3 | 0 | 3 | 3 | 2 | 2 | 2 | 8 | 1 | 4 | 7 | 2 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2, Arm D HL: DUR 1500 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.0 years | 77.0 years | 58.0 years | 68.0 years | 79.0 years | 70.0 years | 68.0 years | 38.0 years | 68.0 years | 73.5 years | 71.0 years | 64.5 years | 60.0 years | 68.0 years | 52.0 years | 61.5 years | 62.0 years | 77.0 years | 51.0 years | 67.0 years |
| Age, Customized < 65 Years | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants | 2 Participants | 1 Participants | 5 Participants | 7 Participants | 2 Participants | 3 Participants | 5 Participants | 1 Participants | 0 Participants | 4 Participants | 44 Participants |
| Age, Customized ≥ 65 Years | 2 Participants | 6 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 6 Participants | 8 Participants | 2 Participants | 5 Participants | 3 Participants | 3 Participants | 2 Participants | 5 Participants | 1 Participants | 5 Participants | 1 Participants | 62 Participants |
| Eastern Cooperative Oncology Group ECOG) Performance Status 0 - Fully Active | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 2 Participants | 8 Participants | 6 Participants | 0 Participants | 6 Participants | 7 Participants | 0 Participants | 2 Participants | 3 Participants | 1 Participants | 4 Participants | 5 Participants | 53 Participants |
| Eastern Cooperative Oncology Group ECOG) Performance Status 1 - Restricted but ambulatory | 1 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 39 Participants |
| Eastern Cooperative Oncology Group ECOG) Performance Status 2 - Ambulatory but unable to work | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 13 Participants |
| Eastern Cooperative Oncology Group ECOG) Performance Status 3 - Limited self-care | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 7 Participants | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 5 Participants | 7 Participants | 2 Participants | 6 Participants | 8 Participants | 3 Participants | 2 Participants | 9 Participants | 2 Participants | 5 Participants | 5 Participants | 76 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 5 Participants | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 28 Participants |
| Histology CLL / SLL | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 18 Participants |
| Histology Diffuse large B-cell lymphoma | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants | 5 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 10 Participants | 0 Participants | 0 Participants | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 37 Participants |
| Histology Follicular lymphoma | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 10 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 23 Participants |
| Histology Hodgkin lymphoma | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Histology Mantle cell lymphoma | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 17 Participants |
| Histology Marginal zone lymphoma | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Histology Transformed follicular lymphoma | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 13 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Collected or Reported | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 27 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 5 Participants | 6 Participants | 2 Participants | 4 Participants | 4 Participants | 4 Participants | 2 Participants | 9 Participants | 2 Participants | 4 Participants | 5 Participants | 63 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 4 Participants | 2 Participants | 2 Participants | 4 Participants | 1 Participants | 2 Participants | 2 Participants | 35 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 7 Participants | 9 Participants | 2 Participants | 7 Participants | 6 Participants | 3 Participants | 3 Participants | 6 Participants | 1 Participants | 3 Participants | 3 Participants | 71 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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 3 | 2 / 8 | 0 / 3 | 3 / 4 | 2 / 3 | 1 / 1 | 3 / 4 | 4 / 5 | 1 / 10 | 2 / 10 | 0 / 10 | 9 / 10 | 2 / 5 | 4 / 5 | 9 / 10 | 0 / 2 | 4 / 5 | 4 / 5 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 8 / 8 | 3 / 3 | 4 / 4 | 3 / 3 | 1 / 1 | 4 / 4 | 5 / 5 | 10 / 10 | 10 / 10 | 10 / 10 | 9 / 10 | 5 / 5 | 5 / 5 | 10 / 10 | 2 / 2 | 5 / 5 | 5 / 5 |
| serious Total, serious adverse events | 1 / 3 | 2 / 3 | 4 / 8 | 2 / 3 | 3 / 4 | 2 / 3 | 1 / 1 | 1 / 4 | 3 / 5 | 6 / 10 | 7 / 10 | 5 / 10 | 5 / 10 | 2 / 5 | 4 / 5 | 8 / 10 | 0 / 2 | 4 / 5 | 2 / 5 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) occurring or worsening on or after the first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. The intensity of AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by the investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5).
Time frame: From first dose of any study drug to 90 days after last dose of durvalumab or 28 days after last dose of other study drugs, up to the data cut-off date of 6 March 2019. Maximum time on treatment was 55.4 weeks for DUR and 130 weeks for other study drugs.
Population: The Safety population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 2 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 2 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 7 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 8 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 7 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 8 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 4 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 3 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 2 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 3 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 2 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 4 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 4 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 3 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 2 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 2 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 2 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 2 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 3 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 3 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 2 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 3 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 5 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 2 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 5 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 10 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 7 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 10 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 6 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 2 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 8 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 8 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 1 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 10 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 7 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 10 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 2 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 9 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 9 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 1 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 6 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 5 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 10 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 7 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 5 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 10 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 6 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 2 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 9 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 9 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 9 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 7 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 5 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 4 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 1 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 2 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 5 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 5 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 5 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 2 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 2 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 4 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 5 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 4 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 4 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 1 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 7 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 0 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 7 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 9 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 2 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 4 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 1 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 2 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 4 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 5 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 3 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 1 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 2 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Related to Any Study Drug | 2 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE | 3 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 1 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 5 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
Primary
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Dose limiting toxicities were evaluated during the DLT evaluation period for participants in the dose finding cohorts. The severity grading was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT is defined as below: Hematologic DLT • Grade 4 neutropenia observed for greater than 5 days duration • Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration • Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement for platelets transfusion • Grade 4 anemia, unexplained by underlying disease • Any other grade 4 hematologic toxicity that does not resolve to participant's pretreatment baseline level within 72 hours. Non-Hematologic DLT • Any non-hematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by medical management • Any treatment interruption greater than 2 weeks due to adverse event.
Time frame: Cycle 1 (28 days)
Population: DLT Evaluable population included participants in Arms A, B, and C of Part 1, who took at least one dose of study drug and completed the DLT evaluation through the end of DLT evaluation period, or participants who took at least one dose of study drug and experienced at least one DLT prior to completion of the DLT evaluation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
Comparison: The safety review committee identified a preliminary recommended Phase 2 dose (RP2D) for each dose finding cohort based on an integrated assessment of the safety, pharmacokinetic, pharmacodynamic, and preliminary efficacy (as available).
Comparison: The safety review committee identified a preliminary recommended Phase 2 dose (RP2D) for each dose finding cohort based on an integrated assessment of the safety, pharmacokinetic, pharmacodynamic, and preliminary efficacy (as available).
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab
Time frame: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
Population: The PK population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab | 4867431.378 days*μg/L | Geometric Coefficient of Variation 23.3 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab | 5818262.846 days*μg/L | Geometric Coefficient of Variation 42.1 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab | 4762968.345 days*μg/L | Geometric Coefficient of Variation 71 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab | 5593532.553 days*μg/L | Geometric Coefficient of Variation 53 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab
Time frame: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
Population: The PK population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab | 3120149.759 days*μg/L | Geometric Coefficient of Variation 29.5 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab | 3225869.344 days*μg/L | Geometric Coefficient of Variation 31.9 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab | 2670168.397 days*μg/L | Geometric Coefficient of Variation 46.7 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab | 3053060.746 days*μg/L | Geometric Coefficient of Variation 37.8 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib
Time frame: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose
Population: PK population with available data
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib | 586.396 h*ng/mL | Geometric Coefficient of Variation 117.2 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib | 436.855 h*ng/mL | Geometric Coefficient of Variation 246.5 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide
Time frame: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose
Population: PK population with available data
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide | 789.297 h*ng/mL | Geometric Coefficient of Variation 84.3 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide | 805.299 h*ng/mL | Geometric Coefficient of Variation 56 |
Secondary
Change From Baseline in Soluble Programmed Cell Death Ligand-1 (sPD-L1) Concentration
Change from baseline in sPD-L1 could not be calculated as all post-baseline samples were below the lower limit of quantification (\<15.60 pg/mL).
Time frame: Baseline (Cycle 1 Day 1 predose) and Day 1 of Cycles 2 to 13
Population: Biomarker Evaluable Population included all participants who received at least 1 dose of study drug and had at least 1 non-missing biomarker assessment. No participants had quantifiable sPD-L1 measurements post-baseline.
Secondary
Clearance (CL) of Durvalumab
Time frame: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
Population: The PK population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Clearance (CL) of Durvalumab | 0.3082 L/day | Geometric Coefficient of Variation 23.3 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Clearance (CL) of Durvalumab | 0.2578 L/day | Geometric Coefficient of Variation 42.1 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Clearance (CL) of Durvalumab | 0.3149 L/day | Geometric Coefficient of Variation 71 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Clearance (CL) of Durvalumab | 0.2682 L/day | Geometric Coefficient of Variation 53 |
Secondary
Kaplan-Meier Estimate of Duration of Response
Duration of response is defined for responders only as the time from the first documented response (CR or PR for lymphoma participants or CR, CRi, nPR, PR, or PRL for CLL participants) to disease progression or death (from any cause). For participants with response but no progression, or death, duration of response was censored at the last date that the participant was known to be progression-free.
Time frame: From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.
Population: Efficacy evaluable population (all participants who completed at least 1 cycle of their assigned treatment, and have baseline and at least 1 post-baseline tumor response assessment) who had an objective response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Kaplan-Meier Estimate of Duration of Response | 10.14 weeks |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Kaplan-Meier Estimate of Duration of Response | NA weeks |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Kaplan-Meier Estimate of Duration of Response | NA weeks |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Kaplan-Meier Estimate of Duration of Response | NA weeks |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Kaplan-Meier Estimate of Duration of Response | NA weeks |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Kaplan-Meier Estimate of Duration of Response | 29.29 weeks |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Kaplan-Meier Estimate of Duration of Response | NA weeks |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Kaplan-Meier Estimate of Duration of Response | NA weeks |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Kaplan-Meier Estimate of Duration of Response | NA weeks |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Kaplan-Meier Estimate of Duration of Response | NA weeks |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Kaplan-Meier Estimate of Duration of Response | 24.14 weeks |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Kaplan-Meier Estimate of Duration of Response | NA weeks |
| Part 2, Arm D HL: DUR 1500 mg | Kaplan-Meier Estimate of Duration of Response | 11.14 weeks |
Secondary
Kaplan-Meier Estimate of Progression-free Survival (PFS)
Progression-free survival was calculated as the time from first dose of study drug to the first documented progression or death (from any cause) during the entire efficacy evaluation period. For participants with no progression or death, PFS was censored at the last assessment date the participant was known to be progression-free.
Time frame: From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.
Population: Safety population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 8.41 months |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Kaplan-Meier Estimate of Progression-free Survival (PFS) | NA months |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Kaplan-Meier Estimate of Progression-free Survival (PFS) | NA months |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Kaplan-Meier Estimate of Progression-free Survival (PFS) | NA months |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 28.71 months |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 9.69 months |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 1.25 months |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 3.82 months |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 2.48 months |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Kaplan-Meier Estimate of Progression-free Survival (PFS) | NA months |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Kaplan-Meier Estimate of Progression-free Survival (PFS) | NA months |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 14.65 months |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 2.06 months |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Kaplan-Meier Estimate of Progression-free Survival (PFS) | NA months |
| Part 2, Arm D FL: DUR 1500 mg | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 1.68 months |
| Part 2, Arm D DLBCL: DUR 1500 mg | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 1.17 months |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 2.76 months |
| Part 2, Arm D MCL: DUR 1500 mg | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 2.33 months |
| Part 2, Arm D HL: DUR 1500 mg | Kaplan-Meier Estimate of Progression-free Survival (PFS) | 2.66 months |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Durvalumab
Time frame: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
Population: The Pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Maximum Observed Plasma Concentration (Cmax) of Durvalumab | 420264.066 μg/L | Geometric Coefficient of Variation 22.7 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Maximum Observed Plasma Concentration (Cmax) of Durvalumab | 361906.229 μg/L | Geometric Coefficient of Variation 30.1 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Maximum Observed Plasma Concentration (Cmax) of Durvalumab | 331572.478 μg/L | Geometric Coefficient of Variation 33.4 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Maximum Observed Plasma Concentration (Cmax) of Durvalumab | 392663.668 μg/L | Geometric Coefficient of Variation 41.1 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Time frame: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.
Population: PK population with available data at each time point
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Cycle 1 Day 1 | 129.704 ng/mL | Geometric Coefficient of Variation 98 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Cycle 1 Day 15 | 86.840 ng/mL | Geometric Coefficient of Variation 136.9 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Cycle 1 Day 1 | 67.728 ng/mL | Geometric Coefficient of Variation 197.9 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Cycle 1 Day 15 | 72.436 ng/mL | Geometric Coefficient of Variation 166.3 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Lenalidomide
Time frame: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.
Population: PK population with available data at each time point
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Maximum Observed Plasma Concentration (Cmax) of Lenalidomide | Cycle 1 Day 1 | 141.881 ng/mL | Geometric Coefficient of Variation 22 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Maximum Observed Plasma Concentration (Cmax) of Lenalidomide | Cycle 1 Day 15 | 107.635 ng/mL | Geometric Coefficient of Variation 40.9 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Maximum Observed Plasma Concentration (Cmax) of Lenalidomide | Cycle 1 Day 1 | 309.917 ng/mL | Geometric Coefficient of Variation 6.9 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Maximum Observed Plasma Concentration (Cmax) of Lenalidomide | Cycle 1 Day 15 | 174.090 ng/mL | — |
Secondary
Overall Response Rate During the Entire Study
For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification) (Cheson, 2014). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percentage of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL).
Time frame: From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.
Population: The Efficacy Evaluable population includes all participants who completed at least 1 cycle of their assigned treatment, and have baseline and at least 1 post-baseline tumor response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Overall Response Rate During the Entire Study | 66.7 percentage of participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Overall Response Rate During the Entire Study | 66.7 percentage of participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Overall Response Rate During the Entire Study | 80.0 percentage of participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Overall Response Rate During the Entire Study | 66.7 percentage of participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Overall Response Rate During the Entire Study | 75.0 percentage of participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Overall Response Rate During the Entire Study | 33.3 percentage of participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Overall Response Rate During the Entire Study | 50.0 percentage of participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Overall Response Rate During the Entire Study | 0 percentage of participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Overall Response Rate During the Entire Study | 100.0 percentage of participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Overall Response Rate During the Entire Study | 70.0 percentage of participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Overall Response Rate During the Entire Study | 88.9 percentage of participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Overall Response Rate During the Entire Study | 30.0 percentage of participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Overall Response Rate During the Entire Study | 50.0 percentage of participants |
| Part 2, Arm D FL: DUR 1500 mg | Overall Response Rate During the Entire Study | 0 percentage of participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Overall Response Rate During the Entire Study | 0 percentage of participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Overall Response Rate During the Entire Study | 0 percentage of participants |
| Part 2, Arm D MCL: DUR 1500 mg | Overall Response Rate During the Entire Study | 0 percentage of participants |
| Part 2, Arm D HL: DUR 1500 mg | Overall Response Rate During the Entire Study | 20.0 percentage of participants |
Secondary
Overall Response Rate (ORR) During Durvalumab Treatment
For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percent of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL).
Time frame: Up to 13 cycles (12 months)
Population: The Efficacy Evaluable population includes all participants who completed at least 1 cycle of their assigned treatment, and have baseline and at least 1 post-baseline tumor response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Overall Response Rate (ORR) During Durvalumab Treatment | 33.3 percentage of participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Overall Response Rate (ORR) During Durvalumab Treatment | 66.7 percentage of participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Overall Response Rate (ORR) During Durvalumab Treatment | 80.0 percentage of participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Overall Response Rate (ORR) During Durvalumab Treatment | 66.7 percentage of participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Overall Response Rate (ORR) During Durvalumab Treatment | 75.0 percentage of participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Overall Response Rate (ORR) During Durvalumab Treatment | 33.3 percentage of participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Overall Response Rate (ORR) During Durvalumab Treatment | 50.0 percentage of participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Overall Response Rate (ORR) During Durvalumab Treatment | 0 percentage of participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Overall Response Rate (ORR) During Durvalumab Treatment | 88.9 percentage of participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Overall Response Rate (ORR) During Durvalumab Treatment | 60.0 percentage of participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Overall Response Rate (ORR) During Durvalumab Treatment | 88.9 percentage of participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Overall Response Rate (ORR) During Durvalumab Treatment | 30.0 percentage of participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Overall Response Rate (ORR) During Durvalumab Treatment | 50.0 percentage of participants |
| Part 2, Arm D FL: DUR 1500 mg | Overall Response Rate (ORR) During Durvalumab Treatment | 0 percentage of participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Overall Response Rate (ORR) During Durvalumab Treatment | 0 percentage of participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Overall Response Rate (ORR) During Durvalumab Treatment | 0 percentage of participants |
| Part 2, Arm D MCL: DUR 1500 mg | Overall Response Rate (ORR) During Durvalumab Treatment | 0 percentage of participants |
| Part 2, Arm D HL: DUR 1500 mg | Overall Response Rate (ORR) During Durvalumab Treatment | 20.0 percentage of participants |
Secondary
Terminal Elimination Phase Half-Life (t½) of Durvalumab
Time frame: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
Population: The PK population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Terminal Elimination Phase Half-Life (t½) of Durvalumab | 11.596 days | Geometric Coefficient of Variation 46.6 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Terminal Elimination Phase Half-Life (t½) of Durvalumab | 17.344 days | Geometric Coefficient of Variation 47.3 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Terminal Elimination Phase Half-Life (t½) of Durvalumab | 16.327 days | Geometric Coefficient of Variation 57.4 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Terminal Elimination Phase Half-Life (t½) of Durvalumab | 15.399 days | Geometric Coefficient of Variation 53.5 |
Secondary
Time to First Response
Time to response was calculated as the time from first dose of study drug to the first response date (CR or PR for lymphoma participants and CR, CRi, nPR, PR, or PRL for CLL participants).
Time frame: From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.
Population: Efficacy evaluable population (all participants who completed at least 1 cycle of their assigned treatment, and have baseline and at least 1 post-baseline tumor response assessment) who had an objective response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Time to First Response | 70.85 weeks |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Time to First Response | 12.60 weeks |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Time to First Response | 18.20 weeks |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Time to First Response | 11.85 weeks |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Time to First Response | 13.40 weeks |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Time to First Response | 13.00 weeks |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Time to First Response | 13.10 weeks |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Time to First Response | 12.10 weeks |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Time to First Response | 12.10 weeks |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Time to First Response | 12.35 weeks |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Time to First Response | 12.00 weeks |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Time to First Response | 12.10 weeks |
| Part 2, Arm D HL: DUR 1500 mg | Time to First Response | 13.10 weeks |
Secondary
Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
Time frame: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.
Population: PK population with available data at each time point
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib | Cycle 1 Day 1 | 2.000 hours |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib | Cycle 1 Day 15 | 1.8833 hours |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib | Cycle 1 Day 1 | 1.9333 hours |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib | Cycle 1 Day 15 | 2.000 hours |
Secondary
Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide
Time frame: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.
Population: PK population with available data at each time point
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide | Cycle 1 Day 1 | 1.9500 hours |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide | Cycle 1 Day 15 | 3.0333 hours |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide | Cycle 1 Day 1 | 1.1667 hours |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide | Cycle 1 Day 15 | 1.000 hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Durvalumab
Time frame: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
Population: PK population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Time to Maximum Plasma Concentration (Tmax) of Durvalumab | 0.0510 days |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Time to Maximum Plasma Concentration (Tmax) of Durvalumab | 0.0479 days |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Time to Maximum Plasma Concentration (Tmax) of Durvalumab | 0.0510 days |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Time to Maximum Plasma Concentration (Tmax) of Durvalumab | 0.0420 days |
Secondary
Volume of Distribution (Vz) of Durvalumab
Time frame: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
Population: The PK population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Volume of Distribution (Vz) of Durvalumab | 5.155 liters | Geometric Coefficient of Variation 41.9 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Volume of Distribution (Vz) of Durvalumab | 6.451 liters | Geometric Coefficient of Variation 38.3 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Volume of Distribution (Vz) of Durvalumab | 7.418 liters | Geometric Coefficient of Variation 33.7 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Volume of Distribution (Vz) of Durvalumab | 5.957 liters | Geometric Coefficient of Variation 33 |
Post Hoc
Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection
TEAEs defined as AEs occurring or worsening on or after first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. Intensity of AEs graded according to the NCI CTCAE V. 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5). This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date (assessments made until August 21, 2022).
Time frame: From first dose of any study drug to 90 days after last dose of durvalumab or 28 days after last dose of other study drugs, up to the study completion date of August 21, 2022 (up to approximately 75 months).
Population: The Safety population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 2 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 2 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 8 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 7 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 7 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 5 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 8 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 4 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 2 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 2 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 3 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 4 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 3 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 4 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 4 Participants |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 2 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 3 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 3 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 2 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 2 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 3 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 2 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 2 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 4 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 5 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 5 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 3 Participants |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 4 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 6 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 8 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 9 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 10 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 10 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 9 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 2 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 9 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 9 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 6 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 10 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 1 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 1 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 10 Participants |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 7 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 2 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 5 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 6 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 7 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 10 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 5 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 10 Participants |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 7 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 5 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 9 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 9 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 9 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 4 Participants |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 5 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 5 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 2 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 1 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 2 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 5 Participants |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 4 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 4 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 2 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 1 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 4 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 5 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Part 2, Arm D FL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 7 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 2 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 4 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 1 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 9 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 0 Participants |
| Part 2, Arm D DLBCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 7 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 1 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 2 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 0 Participants |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 1 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 4 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 3 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 5 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 1 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 3 Participants |
| Part 2, Arm D MCL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Any TEAE | 5 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE Related to Any Study Drug | 1 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Discontinuation of Any Study Drug | 0 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE | 2 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Leading to Dose Modifications of Study Drug | 3 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE Related to Any Study Drug | 0 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | TEAE Related to Any Study Drug | 2 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 5 TEAE | 0 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | CTCAE Grade 3-4 TEAE | 3 Participants |
| Part 2, Arm D HL: DUR 1500 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection | Serious TEAE Related to Any Study Drug | 0 Participants |