Phase 2 registrational study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory multiple myeloma: Updated results from iMMagine–1

Abstract

Abstract Background: Anitocabtagene autoleucel (anito-cel) is an autologous anti–BCMA chimeric antigen receptor (CAR) T-cell therapy with a novel D-domain binder under development for patients (pts) with relapsed and/or refractory multiple myeloma (RRMM). D-Domain attributes, including small size, simple structure, and fast off-rate, facilitate high transduction efficiency, stable CAR expression, and decreased risk of tonic signaling. In the Phase 1 trial (NCT04155749), at a median follow-up of 38.1 months, the median PFS was 30.2 months for all pts and 34.3 months for pts achieving a complete response (CR) or better, and no delayed or non-ICANS neurotoxicities or immune effector cell (IEC)-associated enterocolitis have been observed. Updated results from the fully enrolled, ongoing iMMagine-1 Phase 2 registrational trial (NCT05396885) are presented in this report. Methods: Eligible pts were ≥18 years, triple-class exposed, had progressed after ≥3 LoT, had measurable disease, and were refractory to their last LoT. Following leukapheresis, optional bridging, and anito-cel manufacturing, pts received lymphodepletion chemotherapy and a single infusion of anito-cel (target dose of 115×106 CAR+ T cells). The primary endpoint is overall response rate (ORR) by Independent Review Committee (IRC) and assessed using 2016 International Myeloma Working Group (IMWG) criteria. MRD is assessed by next-generation sequencing, toxicity is graded per CTCAE version 5.0, and CRS and ICANS are graded by the ASTCT consensus criteria. This analysis reports the investigator-assessed safety and efficacy outcomes for all pts infused with anito-cel in the iMMagine-1 trial. Results: At a data cut-off of May 1, 2025, 117 pts had received anito-cel under the final manufacturing process with a median follow-up of 12.6 months. Median age was 64 years (range, 38 -78) and racial distribution was 89 (76%) White, 17 (15%) Black or African American, and 11 (9%) Asian or Other. Median time from MM diagnosis was 7.2 years (range, 1.0 - 23.1), and median prior LoT was 3 (range, 3 - 8) with 51% receiving only 3 prior LoT. All pts (n=117, 100%) were refractory to their last LoT, 100 (86%) were triple-class refractory, 47 (40%) were penta-drug refractory, 18 (15%) had extramedullary disease, and 44 (38%) had high-risk cytogenetics. Ten pts (9%) received outpatient infusion of anito-cel. Investigator-assessed ORR per IMWG criteria was 97% (114/117) with a CR/sCR rate of 68% (79/117) with a median time to first response of 1.0 month (range, 0.9 - 13.4). Of those evaluable for MRD testing (n=75), 70 (93%) achieved MRD negativity at the level of 10-5 with a median time to MRD negativity of 1.0 month (range, 0.9 – 6.4), and MRD negativity at the level of 10-6 was achieved in 78% (53/68). Using Kaplan-Meier methods, the PFS rates at 12- and 18-month milestone timepoints were 79% and 66%, respectively, with 12- and 18-month OS rates being 95% and 90%, respectively. Median PFS and OS have not been reached. The most common grade 3/4 treatment emergent adverse events (AEs) were cytopenias: 77 pts (66%) with neutropenia, 28 (24%) with anemia, and 28 (24%) with thrombocytopenia. Grade 3/4 infections were reported in 11 pts (9%). Ninety-nine pts (85%) had CRS Gr1 or less, including 17 (15%) with no CRS, and 114 (97%) had either no CRS or CRS resolution ≤10 days of anito-cel infusion. Any grade CRS was observed in 100 pts (85%) with 82 (70%) Gr1, 17 (15%) Gr2, and 1 (1%) Gr5. Median onset was 4 days (range, 1-17) with a median duration of 2 days (range, 1-9). Any grade ICANS was observed in 9 pts (8%) with 4 (3%) Gr1, 4 (3%) Gr2, and 1 (1%) Gr3. No delayed or non-ICANS neurotoxicities including no Parkinsonism, no cranial nerve palsies, and no Guillain-Barré syndrome have been observed. No IEC-associated enterocolitis and no secondary primary malignancies of T-cell origin have been reported. Conclusions: Ongoing results from the Phase 2 iMMagine-1 trial demonstrate deep and durable efficacy and manageable safety in a heavily pre-treated, refractory 4L+ RRMM population. No delayed or non-ICANS neurotoxicities including no Parkinsonism, no cranial nerve palsies, no Guillain-Barré syndrome, and no IEC-associated enterocolitis have been observed across the Phase 1 or Phase 2 iMMagine-1 studies to date. Updated data including safety and efficacy outcomes in all patients at a later data cut-off date will be presented.