印度首例，一项针对复发或难治性多发性骨髓瘤的本土化改良、经济高效的自体双靶点BCMA/CD19 CAR T细胞疗法的1/2期研究

Background: B-cell maturation antigen (BCMA) directed CAR T-cell therapies have transformed the treatment landscape of relapsed or refractory multiple myeloma (R/R MM); however, access remains limited in low- and middle-income countries due to high manufacturing costs, logistical complexity, and reliance on imported products. Dual targeting of BCMA and CD19 offers a biologically rational strategy to mitigate antigen escape and disease heterogeneity. VL-2511, an autologous BCMA-CD19 dual-targeted CAR-T cell therapy has been adopted indigenously to enable efficient, scalable, and cost-effective manufacturing for the Indian market. VL-2511 has previously demonstrated compelling clinical activity in patients treated in China (NCT06223646 & NCT04714827) and is currently under global clinical development across multiple geographies, including the United States. Methods: This open-label, multicenter Phase 1/2 study evaluates the safety, feasibility, and preliminary efficacy of VL-2511 in adults with heavily pretreated R/R MM. Following leukapheresis, CAR T-cells are manufactured using a lentiviral vector and an optimized, locally implemented GMP process designed to improve turnaround time, throughput, and affordability. After standard lymphodepletion, patients receive a single CAR T-cell infusion across a predetermined dose levels or at the recommended Phase 2 dose. The primary objective is to assess the efficacy, as measured by the ORR and other clinically relevant efficacy endpoints in accordance with IMWG criteria. Secondary objectives include characterization of the pharmacokinetic and pharmacodynamic profiles of CAR-T cells, assessment of CAR-T cell expansion and persistence, including the incidence and severity of CRS and ICANS. Results: Clinical data from over 35 Patients (and ongoing) have shown compelling efficacy, with an overall response rate (ORR) of 96.6%, and 89.7% CR/sCR, supported by a favorable safety profile. The regulatory review of the clinical protocol and manufacturing activities in India are ongoing and planned in accordance with applicable regulatory requirements. Data relating to protocol implementation, safety assessments, manufacturing feasibility, pharmacokinetics, and preliminary clinical activity will be collected and, if available, will be presented at the meeting. Reported outcomes will include evaluation of product manufacturability using the indigenously adapted process and early clinical observations. Conclusions: This study represents first-in-India clinical evaluation of VL-2511 with an objective to assess efficient, cost-conscious, local manufacturing and delivery of clinically promising Dual CAR T. This approach has the potential to meaningfully expand access to advanced cellular therapies in India and other resource-constrained settings. Beyond R/R MM, and B-cell NHL, the dual-targeted VL-2511 has broader applicability across additional immune-mediated and plasma cell-driven disorders, including POEMS syndrome (NCT06518876), systemic lupus erythematosus, myasthenia gravis, and AL amyloidosis.