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.

Freeman:ONK therapeutics: Consultancy; Seattle Genetics: Consultancy; BMS: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Research Funding; Abbvie: Consultancy; Roche/Genentech: Research Funding; Amgen: Consultancy; Sanofi: Consultancy; Celgene: Consultancy; Incyte: Consultancy. Dhakal:Sanofi: Research Funding; Janssen: Honoraria, Research Funding, Speakers Bureau; Acrellx: Research Funding; Pfizer: Consultancy, Honoraria, Speakers Bureau; Carsgen: Research Funding; C4 therapeutics: Research Funding; Medical College of Wisconsin: Current Employment; Genentech: Consultancy, Honoraria; Karyopharm: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding. Kaur:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellectar Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Arcellx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria. Maziarz:Athersys: Other: participated in data and safety monitoring boards, Patents & Royalties; Orca: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Novartis: Consultancy, Other: participated in data and safety monitoring boards , Research Funding; Ori-cell Therapeutic: Honoraria; Gilead Sciences: Other: stock or other ownership; Artiva Bio: Other: Leadership Role; stock or other ownership; Bristol Myers Squibb: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy; Autolus: Consultancy; Vor BioPharma: Other: participated in data and safety monitoring boards; Century Therapeutics: Other: participated in data and safety monitoring boards. Sperling:Novartis: Consultancy. Schinke:Arcellx: Consultancy; Cancer Network: Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; OncLive: Honoraria. Biran:AbbVie: Consultancy; Sanofi: Honoraria, Speakers Bureau; Amgen: Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharm: Research Funding; Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau. Sborov:Arcellx: Consultancy; Parexel, Keosys: Other: IRC; Pfizer: Consultancy, Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; Bioline: Consultancy; Society of Utah Medical Oncology: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; University of Utah, Huntsman Cancer Institute: Current Employment; Janssen: Consultancy; Legend Biotech: Consultancy; Bristol Myers Squibb: Consultancy; GlaxoSmithKline: Consultancy; Sanofi: Consultancy; Binaytara Foundation: Honoraria. Varga:Janssen: Consultancy, Research Funding; LavaTherapeutics: Research Funding. Deol:Kite, a Gilead Company: Consultancy; Adicet Biotherapeutics: Consultancy; Janssen: Consultancy. Kanate:IOVANCE: Other: stock or other ownership; Kite, a Gilead Company: Speakers Bureau; ADC Therapeutics: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Koçoğlu:GlaxoSmithKline: Other: research funding (to institution) from, Research Funding; Takeda: Other: research funding (to institution) from, Research Funding; Poseida: Other: research funding (to institution) from, Research Funding; Caelum: Other: research funding (to institution) from, Research Funding; Arcellx: Research Funding; Celgene/Bristol Myers Squibb: Other: research funding (to institution) from, Research Funding; Janssen: Other: research funding (to institution) from, Research Funding. Solh:Bristol Myers Squibb: Consultancy, Speakers Bureau; GlaxoSmithKline: Speakers Bureau; Sanofi: Consultancy. Banerjee:Arcellx: Current Employment, Other: stock ownership. Chan:Arcellx: Current Employment; Gilead Sciences: Other: stock or other ownership in. Nahas:Kite, a Gilead Company and Lantern: Current Employment, Other: stock or other ownership; Lantern: Other: immediate family member. Kostic:Arcellx: Current Employment, Other: stock ownership. Granados:Kite, A Gilead Company: Current Employment, Other: stock ownership. Jackson:Kite, a Gilead Company: Current Employment, Other: travel, accommodation and expenses; Johnson & Johnson (2018-2023): Ended employment in the past 24 months, Other: other intellectual property, and travel, accommodation and expenses , Patents & Royalties; Memorial Sloan Kettering Cancer Center: Consultancy, Other: Physician Consultant. Heery:Arcellx: Current Employment, Other: leadership role at, and stock or other ownership . Welliver:Arcellx: Current Employment, Other: stock or other ownership . Patel:Abbvie: Consultancy; Poseida: Consultancy; BMS: Consultancy, Other: chair of scientific advisory board ; Kite, A Gilead company: Consultancy, Other: scientific advisory board; Takeda: Consultancy; Merck: Consultancy; Johnson & Johnson (Janssen): Consultancy; Genentech: Consultancy; AstraZeneca: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; Caribou Sciences: Consultancy; Oricel: Consultancy, Other: Chair of scientific board. Frigault:Novartis: Consultancy; Kite, a Gilead Company: Consultancy; Bristol Meyers Squibb: Consultancy; JNJ/Legend: Consultancy; Cytoagents: Consultancy; Iovance: Consultancy; SOBI: Research Funding.