Background: For pts with DLBCL who fail 1^st-line therapy, the only potentially curative treatment is salvage chemotherapy followed by autologous stem cell transplant (ASCT). Only »50% of pts receiving salvage chemotherapy proceed to ASCT and 3-y progression-free survival (PFS) is 53% after ASCT (Gisselbrecht et al. JCO. 2010). In ZUMA-1, the pivotal, single-arm study of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, the objective response rate (ORR) was 82% (58% complete response [CR] rate) in pts with refractory large B cell lymphoma; 40% remained in CR with 15.4-mo median follow-up (Neelapu & Locke et al. NEJM. 2017). This trial was primarily in pts with ≥ 2 prior lines of therapy and supported US FDA approval of axi-cel for the treatment of adult pts with R/R DLBCL after ≥ 2 prior lines of systemic therapy. ZUMA-7 investigates axi-cel as 2^nd-line therapy for pts with R/R DLBCL. Methods: ZUMA-7 (NCT03391466) is a randomized (1:1) Phase 3, open-label, multicenter study of axi-cel vs SOC 2^nd-line treatment in pts with R/R DLBCL. Planned enrollment is 350 pts. Eligible pts must have R/R DLBCL after 1^st-line therapy (including an anti-CD20 antibody and an anthracycline) and intend to proceed to ASCT if they respond to 2^nd-line therapy. Exclusion criteria include prior SCT, prior CD19-targeted therapy, or active infection. Pts randomized to axi-cel will undergo leukapheresis, then lymphodepleting chemotherapy (fludarabine 30 mg/m²/d and cyclophosphamide 500 mg/m²/d for 3 d), followed by a single infusion of axi-cel at 2 × 10⁶ CAR T cells/kg. Corticosteroid bridging therapy is allowed for pts with high disease burden at screening. Pts in the SOC arm will receive investigator’s choice of 2^nd-line salvage therapy (R-ICE, R-DHAP, R-ESHAP, or R-GDP); pts who respond after 2–3 cycles will receive high-dose therapy and ASCT. The primary endpoint is event-free survival defined as time from randomization to disease progression, start of new lymphoma therapy, or death. Secondary endpoints include ORR, overall survival, PFS, duration of response, safety, and pt-reported outcomes. Accrual is ongoing. Clinical trial information: NCT03391466