Arcellx, Inc. (NASDAQ: ACLX) has announced promising new data from its Phase 2 iMMagine-1 study evaluating anitocabtagene autoleucel (anito-cel) in patients with relapsed or refractory multiple myeloma (RRMM). The results, presented at the 66th American Society of Hematology (ASH) Annual Meeting, showcase a high overall response rate and a manageable safety profile, positioning anito-cel as a potential best-in-class treatment option.
The iMMagine-1 study evaluated 86 efficacy-evaluable patients with a median follow-up of 9.5 months. All patients received a single infusion of anito-cel at a target dose of 115 × 10^6 CAR+ viable T cells. The patient population was heavily pre-treated, with 87% being triple refractory and 42% penta refractory, having received a median of four prior lines of therapy.
High Response Rates and MRD Negativity
The study achieved an impressive 97% overall response rate (ORR), with 83 out of 86 patients responding to the treatment. The complete response/stringent complete response (CR/sCR) rate was 62% (53/86), and the very good partial response or higher (>VGPR) rate reached 81% (70/86), according to the International Myeloma Working Group (IMWG) criteria. Furthermore, 93.1% (54/58) of patients evaluable for minimal residual disease (MRD) testing achieved MRD negativity at a minimum sensitivity of 10^-5.
While median progression-free survival (mPFS) and overall survival (OS) were not reached, the 6-month PFS and OS rates were 93.3% and 96.5%, respectively. The 12-month PFS and OS rates were 78.5% and 96.5%, respectively, indicating durable responses.
Favorable Safety Profile
A key highlight of the anito-cel therapy is its safety profile. No delayed or non-ICANS neurotoxicities, including Parkinsonism, cranial nerve palsies, or Guillain-Barré syndrome, have been observed in over 150 patients dosed with anito-cel across the Phase 1 and iMMagine-1 studies. Grade ≤1 cytokine release syndrome (CRS) occurred in 86% of the safety evaluable population (84/98), with 17% experiencing no CRS. The median onset of CRS was four days (range: 1-17 days). 8% of patients were treated as outpatients. Any Grade ICANS was observed in 9% of patients (9/98), with all cases resolving without sequelae.
However, there were three deaths due to treatment-emergent adverse events (TEAEs): retroperitoneal hemorrhage, CRS, and fungal infection. Cytopenias were the most common Grade ≥3 TEAEs, including neutropenia (54%), thrombocytopenia (20%), and anemia (22%).
Clinical Perspective
Ciara Freeman, M.D., Ph.D., from Moffitt Cancer Center, noted, "The data from the iMMagine-1 study demonstrate that this is a highly active product with impressive depth of responses achieved in patients with relapsed or refractory multiple myeloma...the emerging safety profile of anito-cel is encouraging, in particular the absence of any delayed neurotoxicities reported to date."
Ongoing and Future Studies
Arcellx has initiated the iMMagine-3 study, a global Phase 3 randomized controlled trial, to compare anito-cel with standard of care in patients with RRMM who have received one to three prior lines of therapy. This study aims to further establish anito-cel as a differentiated CAR-T treatment option in earlier lines of therapy.
Collaboration with Kite
Arcellx and Kite, a Gilead Company, have a global strategic collaboration and license agreement to co-develop and co-commercialize anito-cel for RRMM. Kite and Arcellx will jointly commercialize anito-cel in the United States, while Kite will handle commercialization outside the United States.
