Rapcabtagene autoleucel for R/R B-ALL: Phase I multicentre study

Results from a phase I trial (NCT03960840), evaluating the safety and efficacy of rapcabtagene autoleucel in adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), were presented by Pere Barba at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US. Patients received single-infusion rapcabtagene autoleucel at one of four targeted dose levels (DLs). The primary endpoints were safety and dose-limiting toxicities (DLTs) to identify a recommended dose. Secondary endpoints included best overall response (BOR) of complete remission (CR) or CR with incomplete blood count recovery (CRi) by Month 3, and duration of response (DoR). At data cutoff, 41 patients were enrolled and 35 received rapcabtagene autoleucel.

Key data: At 27.7 months’ follow-up, 100% of patients experienced ≥1 adverse event (AE) of any grade, 94% had a Grade ≥3 AE, and 74% had a serious AE (SAE). Grade ≥3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 23% and 11% of all patients, respectively. DLTs occurred in 2/10 patients at DL1, 1/6 at DL2, 1/12 at DL3, and none at DL4. Among all patients at Month 3, overall response rate (ORR) was 86% (CR, 49%; CRi, 37%). 3-month BOR was 70% at DL1, 100% at DL2, 92% at DL3, and 83.3% at DL4. Among evaluable patients, minimal residual disease (MRD)-negativity was achieved in 100% of patients at all DLs. Median DoR was 5 months for DL1, 11 months for DL2, and not reached in DL3/DL4. Significant cellular expansion was observed, with levels higher for DL2–4.

Key learning: Rapcabtagene autoleucel shows high cellular expansion, durable efficacy for DL2–4, and a manageable safety profile in adult patients with R/R B-ALL, supporting the continued evaluation of this therapy in this patient population.