This study will evaluate the safety, efficacy, and pharmacokinetics of mosunetuzumab or glofitamab in combination with CELMoDs (CC-220 and/or CC-99282) in participants with B-cell NHL.
Age >/= 18 years
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
History of one of the following histologically documented hematologic malignancies that are expected to express the CD20 antigen: In the Dose Escalation phase, participants must have relapsed after or failed to respond to at least two prior lines of systemic therapy. In the Dose Expansion phase, participants with FL Grades 1-3a must have relapsed after or failed to respond to at least one prior line of systemic therapy and must require systemic therapy. Participants with DLBCL/transformed FL must have relapsed after or failed to respond to at least one prior systemic treatment regimen.
Participants with DLBCL/transformed FL who have received only one prior line of therapy must: Not be considered a candidate for autologous stem cell transplantation (ASCT) due to age, performance status, comorbidities and/or insufficient response to prior treatment, or have refused ASCT; or be ineligible for or unable to receive chimeric antigen receptor T-cell (CAR-T) therapy due to reasons defined by the protocol
Pregnancy or breastfeeding, or intention of becoming pregnant during the study (female participants of childbearing potential must have a negative serum pregancy test result within 14 days prior to initiation of the study treatment) or within 3 months after the final dose of mosunetuzumab, at least 3 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, whichever is longer, 28 days after the last dose of CC-220, 28 days after the last dose of CC-9282, 3 months after the final dose of tocilizumab, whichever is longer
Participant has received prior therapy with cereblon (CRBN)-modulating drug (e.g., lenalidomide, avadomide/CC-122, pomalidomide) </= 4 weeks prior to starting CC-220 and/or CC-99282
Inability to swallow pills, or persistent diarrhea or malabsorption >= Grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), despite medical management
QTc interval of > 470 ms
Parallel
SC Mosunetuzumab
DrugParticipants will receive SC mosunetuzumab for 12 cycles (cycle length = 21 days or 28 days for Cycle 1 and 28 days for Cycles 2-12)
IV Glofitamab
DrugParticipants will receive IV glofitamab for 12 cycles (cycle length = 21 days)
Iberdomide
DrugArm 1: Participants will receive oral CC-220 from Day 1-21 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12)
Golcadomide
DrugArm 1: Participants will receive oral golcadomide from Day 1-14 starting in either Cycle 1 or Cycle 2 through Cycle 12 (cycle length = 28 days for cycles when golcadomide is to be administered) Arm 2: Participants will receive oral golcadomide from Day 1-10 starting in either Cycle 1, Cycle 2 or Cycle 3 through Cycle 12 (cycle length = 21 days)
Obinutuzumab
DrugParticipants in Arm 2 will receive pre-treatment with IV obinutuzumab on Cycle 1 Day 1 (cycle length = 21 days)
Tocilizumab
DrugParticipants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS)
Percentage of participants with dose-limiting toxicities (DLTs) [dose escalation]
Percentage of participants with adverse events [all cohorts]
Best overall response rate (ORR), defined as the proportion of participants whose best overall response is a partial response (PR) or a complete response (CR) during the study, as determined by the investigator using Lugano 2014 criteria [dose expansion]
Tolerability, as assessed by the incidence of dose interruptions, dose reductions, dose intensity, and treatment discontinuation [dose escalation]
Best CR rate, defined as the proportion of participants whose best overall response is a CR during the study, as determined by the investigator using Lugano 2014 criteria [all cohorts]
Best ORR (CR or PR at any time) on study as determined by the investigator using Lugano 2014 criteria [dose escalation]
Duration of response (DOR) as determined by the investigator using Lugano 2014 criteria [all cohorts]
Progression-free survival (PFS) as determined by the investigator using Lugano 2014 criteria [dose expansion]
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