Safety and efficacy profile of a very low dose of MC-1-50 for treatment of r/r NHL.

Abstract

7553 Background: CD19 chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy in the r/r B-NHL. However, many patients fail to respond, or quickly relapse after the initial response. To improve efficacy, we established a novel PrimeCAR platform (PRIMCAR) that shortens the manufacture time to about 2 days and enriches more stem cell-like memory T (Tscm) cells in the product. The MC-1-50 CAR-T cells produced by the PRIMCAR platform have exhibited a promising efficacy for B-ALL (Shiqi Li, et al. J Clin Oncol 2022; 40 [suppl 16]. Abstract 7008). Here, we report the preliminary safety and efficacy data of MC-1-50 for r/r B-NHL. Methods: In this Phase I /II study (NCT04271410), MC-1-50 CAR T cells were manufactured by the PRIMCAR platform. T cells were infected with a lentiviral vector encoding a humanized CD19 specific scFv following 4-1BB and CD3ζ cytoplasmic domain. Patients (pts) received single-dose of MC-1-50 at dose ranged 0.5-5×105 CAR+/kg (Level 1, 0.5×105 CAR+/kg; Level 2, 3×105 CAR+/kg; Level 3, 5×105 CAR+/kg). Pts were pre-conditioned with fludarabine (25-30 mg/m2) and cyclophosphamide (200-300 mg/m2) daily for 3 days. Toxicity was graded by CTCAE, CRS and ICANS were graded by ASTCT criteria. Primary endpoints are the dose-limiting toxicities (DLTs) rate in the first 28 d and safety to determine a recommended Phase II dose (RP2D). Results: As of May 2022, thirteen pts with r/r B-NHL were infused with MC-1-50. Disease characteristics and outcomes are shown in the table. No DLTs were reported. 3 pts (23.08%) experienced CRS, including 2 (15.38%) at grade 1, and 1 (7.69%) at grade 2, no ≥ 3 CRS were observed, and no ICANS occurred. A preliminary dose-dependent response was observed. At dose Level 1 (DL1), none of the 3 patients showed a good response. At DL2, two patients showed PR response, and 3 of the 5 patients achieved CR response. At DL3, 5 of 5 patients achieved CR response. These patients with CR response did not experience a relapse during the followed-up (ranging from 5-18 months). CAR-T expansion was observed in all dose levels, although long-term persistence cannot be evaluated yet, 4 of 5 patients in DL2 and 3 of 5 patients in DL3 had detectable CAR expression by qPCR (≥50 copy/ ug DNA) in the 6-month follow-up. Conclusions: The PRIMCAR platform could produce CAR T cells quickly with a high percentage of Tscm. Treatment of r/r B-NHL at very low dose resulted in excellent safety profiles while exhibiting a high and durable efficacy. Clinical trial information: NCT04271410 . [Table: see text]