The purpose of this study is to evaluate the safety and efficacy of glofitamab, as monotherapy and in combination with a standard chemoimmunotherapy regimen: rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in pediatric and young adult participants with relapsed and refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL).
Age 6 months to < 18 years at the time of signing Informed Consent for Cohort A Part 1 and Cohort B of the study, and age 6 months to < 30 years old at the time of signing Informed Consent for Cohort A Part 2 of the study
Histologically re-confirmed diagnosis, via tissue biopsy, or bone marrow aspirate, pleural effusion, or ascites, prior to study entry of aggressive mature B-NHL that expresses CD20 (reconfirmed by IHC or flow cytometry if IHC is not possible), including BL, BAL (mature B-cell leukemia FAB L3), DLBCL, and PMBCL, at the time of first R/R disease for Cohort A and second or greater R/R disease for Cohort B
Refractory or relapsed disease (i.e., prior treatment was ineffective or intolerable) following first-line standard-of-care chemoimmunotherapy for Cohort A and following at least two prior systemic chemoimmunotherapy regimens and who have exhausted all available established therapies for Cohort B
Measurable disease, defined as: At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension; or percentage of bone marrow involvement with lymphoma cells defined by cytomorphological analysis of bone marrow aspirates
Isolated CNS disease of mature B-NHL without systemic involvement, and primary CNS lymphoma
Receipt of glofitamab prior to study enrollment
Ongoing adverse events from prior anti-cancer therapy that were not resolved to Grade ≤ 1 (exceptions: alopecia, Grade 2 peripheral neuropathy)
Grade ≥ 3 adverse events, with the exception of Grade 3 endocrinopathy managed with replacement therapy
Parallel
Obinutuzumab
DrugParticipants will receive intravenous (IV) obinutuzumab pretreatment on Days 1 and 2 of Cycle 1 (Cycle length = 21 days)
Glofitamab
DrugArm A: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of Cycles 2 and 3 Arm B: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of each cycle thereafter (Cycle length = 21 days)
Rituximab
DrugParticipants will receive IV rituximab on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)
Ifosfamide
DrugParticipants will receive IV ifosfamide on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)
Carboplatin
DrugParticipants will receive IV carboplatin on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)
Etoposide
DrugParticipants will receive IV etoposide on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)
Tocilizumab
DrugParticipants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events
Achievement of a complete response (CR) as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants (Arm A)
Percentage of participants with adverse events (AEs) (Arm A)
Serum concentration of glofitamab in combination with R-ICE chemoimmunotherapy (Arm A)
Serum concentration of glofitamab monotherapy (Arm B)
Objective response rate (ORR) (Arms A and B)
Duration of complete response (DOCR) (Arm A)
Progression-free survival (PFS) (Arm A)
Event-free survival (EFS) (Arm A)
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