Phase 2 Registrational Study of Anitocabtagene Autoleucel for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Preliminary Results from the IMMagine-1 Trial

Background: Anitocabtagene autoleucel (anito-cel, previously CART-ddBCMA) is an autologous anti–B-cell maturation antigen (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). Results from the Phase 1 study in pts with RRMM who had ≥3 prior lines of therapy (LoT; 4L+; N=38) demonstrated an overall response rate (ORR) of 100%, a complete response (CR)/stringent CR (sCR) rate of 76%, and an estimated 24-month progression-free survival (PFS) rate of 56% (Frigault MJ, et al. ASH 2023). Initial results from the ongoing iMMagine-1 Phase 2 registrational trial (NCT05396885) are presented in this report.

Methods: Eligible triple-class–exposed pts ≥18 years with RRMM who progressed after ≥3 prior LoT with evidence of measurable disease, and were refractory to their last LoT, were enrolled. Following leukapheresis, optional bridging, and anito-cel manufacturing, pts received lymphodepletion chemotherapy (fludarabine 30 mg/m²/d and cyclophosphamide 300 mg/m²/d for 3 days) and a single infusion of anito-cel (target dose of 115×10⁶ CAR+ viable T cells). The primary endpoint of the study is to determine the efficacy of anito-cel, assessed by ORR (sCR, CR, very good partial response [VGPR], and partial response [PR]), as determined by an independent review committee. Efficacy outcomes were assessed using 2016 International Myeloma Working Group (IMWG) criteria, minimal residual disease (MRD) was assessed by next-generation sequencing (sensitivity threshold, 10^-5), toxicity was graded per Common Terminology Criteria for Adverse Events version 5.0, and cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded by the American Society for Transplantation and Cellular Therapy consensus criteria. This preliminary analysis of pts with ≥2 months of follow-up after anito-cel infusion reports investigator-assessed safety and efficacy outcomes.

Results: As of June 1, 2024, 58 pts had received anito-cel infusion under the final manufacturing process with ≥2 months of follow-up after infusion; median follow-up was 10.3 months (range, 2.0-17.8). Median age was 66 years (range, 38-77). Pts had received a median of 4 prior LoT (range, 3-8) with 26 pts (45%) having received only 3 prior LoT. Forty pts (69%) were triple-class refractory and 20 (34%) were penta-class refractory. Investigator-assessed ORR per IMWG criteria was 95% (55/58) with a CR/sCR rate of 62% (36/58). Of those evaluable for MRD testing (n=39), 36 (92%) achieved MRD negativity at least to the level of 10^-5. The Kaplan–Meier-estimated 6-month PFS and overall survival (OS) rates (95% CI) were 90% (77-96) and 95% (85-98), respectively; median PFS and OS have not yet been reached.

Any grade (Gr) CRS was observed in 49 pts (84%). Notably, 46 pts (79%) had either no CRS (n=9, 16%) or Gr 1 CRS (n=37, 64%). Additionally, Gr 2 CRS events occurred in 11 pts (19%), and 1 pt (2%) had a Gr 5 CRS event. The median time to CRS onset was 2 days (range, 1-17) with a median duration of 3 days (range, 1-9). Of note, 31 pts (53%) had no fever or CRS in the first 3 days of anito-cel.

Any Gr ICANS was observed in 5 pts (9%): 2 (3%) Gr 1, 2 (3%) Gr 2, and 1 (2%) Gr 3 events. Median time to ICANS onset was 5 days (range, 2-7) with a median duration of 6 days (range, 1-10); all cases resolved without sequelae. No delayed neurotoxicity, cranial nerve palsies, Guillain Barre syndrome, or Parkinsonian-like symptoms were observed. Cytopenias were the most common Gr ≥3 treatment-emergent adverse events (AEs); 36 pts (62%) had Gr ≥3 neutropenia, 15 (26%) had Gr ≥3 thrombocytopenia, and 15 (26%) had Gr ≥3 anemia. Three deaths occurred due to AEs (both related and unrelated; retroperitoneal hemorrhage, CRS, fungal infection).

Conclusions: Preliminary results from the first 58 pts in the Phase 2 iMMagine-1 trial demonstrate deep and durable efficacy and manageable safety in a high-risk 4L+ RRMM population including triple- and penta-class refractory disease. Notably, no delayed neurotoxicity, cranial nerve palsies, Guillain Barre syndrome, or Parkinsonian-like symptoms were observed in the Phase 1 study or in the Phase 2 iMMagine-1 study to date. Updated data with additional follow-up will be presented.