Preliminary safety and efficacy of relmacabtagene autoleucel (relma-cel) as second-line therapy for primary refractory Chinese patients with large B-cell lymphoma (LBCL): Results from an open-label, multicenter, single-arm phase I study.

e19509 Background: Relmacabtagene autoleucel (relma-cel) is a CD19-directed 4-1BB/CD3ζ chimeric antigen receptor T cell (CAR-T) product manufactured in China, it had been approved by NMPA for treatment of adults with r/r LBCL after ≥2 lines of systemic therapies based on the pivotal study (NCT04089215). Here, we report the results of relma-cel in patients with primary refractory disease after first-line standard of care (R-CHOP), an indication with poor clinical outcomes. Methods: This was an open-label, single-arm, multi-center, phase I study (NCT04812691). Eligible adults (≥18 years) met the criteria for primary refractory LBCL (not reach CR after first-line therapy). After screening and leukapheresis, patients received lymphodepletion [cyclophosphamide/fludarabine] followed by 100×10 6 CAR+ T cells. Results: High-risk disease characteristics were common in the study (Table). As of Nov 26, 2021, 14 patients had leukapheresis and 12 had relma-cel infusion. Among the efficacy-evaluable patients, the best ORR and CRR was 75.0% (95% CI: 42.8-94.5%) and 33.3% (95% CI: 9.9-65.1%), 3-month ORR and CRR were 41.7% (95% CI: 15.2-72.3%) and 33.3% (95% CI: 9.9-65.1%), respectively. With a median follow-up of 9.1 months, the median PFS was 10.0 months (95% CI: 0.85, NA), median DOR and OS were NA (95% CI: 2.2, NA) and NA (95% CI: 3.2, NA). Treatment-emergent adverse events (TEAE) were found in all patients. 10 (83.3%) patients had 1 or more study related Gr ≥3 TEAEs, the most common was cytopenia. 6 (50.0%) patients had Gr ≥3 prolonged cytopenia at Day 29. 6 (50.0%) patients had Gr ≤ 2 Cytokine Release Syndrome (CRS) with a median onset and duration of 6.0 and 11.0 days, no Gr ≥3 CRS observed. Neurotoxicity (NT) occurred in 2 patients (all Gr 1), the median onset and duration was 15.0 and 6.0 days. 2 deaths occurred in study due to disease progression. For 12 PK-evaluable patients, median Cmax was 36762.5 copies/μg DNA by qPCR with a median Tmax of 11 days and a median AUC1-29 of 333459.3 day×copies/μg. In 6 patients whose CAR-T cell had reached BLQ, 5 (83.3%) still had response with 4 (66.7%) patients for CR, 1 (16.7%) patients for PR. Univariate analysis did not indicate association between response and either exposure (AUC1–29) or peak concentration. Conclusions: Relma-cel was tolerable and showed promising ORR in Chinese patients with primary refractory LBCL. Evaluation of relma-cel in high risk second-line LBDL patients using a randomized trial design is planned. Clinical trial information: NCT04812691. [Table: see text]