A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitamab in Combination With CC-220 and CC-99282 in Participants With B-Cell Non-Hodgkin Lymphoma

A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitamab in Combination With CC-220 and CC-99282 in Participants With B-Cell Non-Hodgkin Lymphoma

A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitamab in Combination With CC-220 and CC-99282 in Patients With B-Cell Non-Hodgkin Lymphoma

This study will evaluate the safety, efficacy, and pharmacokinetics of mosunetuzumab or glofitamab in combination with CELMoDs (CC-220 or CC-99282) in participants with B-cell NHL.

Participants will receive SC mosunetuzumab for 12 cycles (cycle length = 21 days for Cycle 1 and 28 days for Cycles 2-12)

Arm 1: Participants will receive oral CC-220 from Day 1-21 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12)

Arm 1: Participants will receive oral CC-99282 from Day 1-14 of Cycle 2-12 (cycle length = 28 days for Cycles 2-12) Arm 2: Participants will receive oral CC-99282 from Day 1-10 of Cycle 3-12 (cycle length = 21 days)

Participants in Arm 2 will receive pre-treatment with IV obinutuzumab on Cycle 1 Day 1 (cycle length = 21 days)

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]

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]

Event-free survival (EFS) as determined by the investigator using Lugano 2014 criteria [dose expansion]

Inclusion Criteria: 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, patients with R/R NHL who previously received at least two prior lines of systemic therapies can be enrolled. In the Dose Expansion phase, patients with FL (grade 1-3a), DLBCL/transformed FL who failed to respond to at least one prior line of systemic therapy can be potentially enrolled Fluorodeoxyglucose-avid lymphoma (i.e. PET-positive lymphoma) At least one bi-dimensionally measurable nodal lesion (> 1.5 cm in its largest dimension by diagnostic quality CT or PET/CT scan), or at least one bi-dimensionally measurable extranodal lesion (> 1.0 cm in its largest dimension by diagnostic quality CT or PET/CT scan) Availability of a representative tumor specimen and the corresponding pathology report for confirmation of the diagnosis of NHL A fresh pretreatment biopsy during screening period, excisional or incisional, is preferred Adequate hematologic function without growth factors or blood product transfusion within 14 days of first dose of study drug administration Normal laboratory values All participants and health care providers will be trained and counseled on pregnancy prevention. For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 3 months after the final dose of mosunetuzumab, at least 18 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, 28 days after the last dose of CC-220, 6 months and 2 weeks after the last dose of CC-99282, 3 months after the last dose of tocilizumab (if applicable), whichever is longer For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for at least 3 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, 90 days after the last dose of CC-220, 3 months and 2 weeks after the last dose of CC- 99282, 2 months after the final dose of tocilizumab (if applicable), whichever is longer Exclusion Criteria: 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) 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 The following treatments prior to study entry: mosunetuzumab, glofitamab, or other CD20/CD3-directed bispecific antibodies; allogenic stem cell therapy (SCT); solid organ transplantation Treatments (investigation or approved) within the following time periods prior to initiation/first dose of study treatment: radiotherapy within 2 weeks; autologous SCT within 100 days; chimeric antigen receptor (CAR) T-cell therapy within 30 days; prior anti-lymphoma treatment with monoclonal antibodies or antibody-drug conjugates within 4 weeks; use of radioimmunoconjugates within 12 weeks; systemic immunosuppressive medications within 2 weeks; any other anti-cancer therapy, whether investigational or approved, including but not limited to chemotherapy, within 4 weeks or 5 half-lives of the drug, whichever is shorter Live, attenuated vaccine within 4 weeks before first dose of study treatment, or in whom it is anticipated that such a live attenuated vaccine will be required during the study period or within 5 months after the final dose of study treatment Current or past history of central nervous system (CNS) lymphoma or leptomeningeal infiltration History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins) History of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis Major surgery or significant traumatic injury < 28 days prior to enrollment (excluding biopsies) or anticipation of the need for major surgery during study treatment Clinically significant toxicities from prior treatment have not resolved to Grade </= 1 (per US national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) v5.0) prior to the first study drug administration with exceptions defined by the protocol Evidence of any significant, concomitant disease (e.g. cardiovascular, pulmonary, liver, CVA or stroke, ILD, PML, infection, HLH etc) that could affect compliance with the protocol or interpretation of results For participants enrolled into glofitamab cohort: documented refractoriness to an obinutuzumab monotherapy-containing regimen (defined as disease that did not achieve response (PR or CR) or progressed within 6 months of the last dose of an obinutuzumab-containing regimen)

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