This is a global, open-label, multi-arm, parallel multi-cohort, multi-center, Phase 1/2 study to determine the safety, tolerability, PK, efficacy and patient-reported quality of life of JCAR017 in combination with various agents. This protocol is intended to evaluate various drug combinations with JCAR017, as separate arms, over the life of the protocol, using the same objectives. Each combination will be evaluated separately (ie, the intention is not to compare between combinations) for the purposes of the objectives, trial design, and statistical analysis. The following combinations will be tested: Arm A: JCAR017 in combination with durvalumab Arm B: JCAR017 in combination with CC-122 (avadomide) Arm C: JCAR017 in combination with CC-220 (iberdomide) Arm D: JCAR017 in combination with ibrutinib Arm E: JCAR017 in combination with relatlimab and/or nivolumab Arm F: JCAR017 in combination with CC-99282 Additional arms will be added by way of amendment once combination agents have been selected. The study will consist of 2 parts: dose finding (Phase 1) and dose expansion (Phase 2). Dose expansion may occur in one or more arms.

During Phase 1, different arms may be opened to test JCAR017 in combination with combination agent(s) in adult subjects with R/R aggressive B-cell NHL. Within each arm, different doses and schedules of JCAR017 and the combination agent(s) may be tested in several cohorts and subcohorts per arm. During Phase 2 of the study, the expansion of any dose level and schedule for any arm that has been shown to be safe may occur. Arm A will test JCAR017 in combination with Durvalumab Arm B will test JCAR017 in combination with CC-122 Arm C will test JCAR017 in combination with CC-220 (iberdomide ) Arm D will test JCAR017 in combination with ibrutinib. Arm E will test JCAR017 in combination with relatlimab and/or nivolumab Arm F will test JCAR017 in combination with CC-99282 All subjects from Phase 1 and Phase 2 will be followed for 24 months following JCAR017 infusion. Post-study follow-up for survival, relapse, long-term toxicity (including new malignancies), and viral vector safety will continue under a separate long-term follow-up (LTFU) protocol for up to 15 years after the JCAR017 dose as per health authority regulatory guidelines.