Introduction: MagnetisMM-1 (NCT03269136) is a Phase 1 study of elranatamab (PF-06863135), a humanized bispecific molecule that targets BCMA expressed on multiple myeloma (MM) and engages CD3 on T cells, for patients (pts) with relapsed or refractory MM (RRMM). We report results from the subcutaneous (SC) cohorts: dose escalation (Part 1), monotherapy with priming (Part 1.1), lenalidomide (LEN) combination (Part 1C), pomalidomide (POM) combination (Part 1D), and monotherapy expansion with priming (Part 2A).

Methods: In Part 1, pts received elranatamab at 80, 130, 215, 360, 600, and 1000μg/kg weekly guided by a modified toxicity probability interval method. For monotherapy at the recommended Phase 2 dose (RP2D; Parts 1.1 and 2A), a single priming dose (600μg/kg or equivalent fixed dose of 44mg) was followed one week later by the full dose (1000μg/kg or equivalent fixed dose of 76mg) weekly (Q1W) or every 2 weeks (Q2W) thereafter. For LEN or POM combination therapy, a single priming dose (32mg) was followed one week later by the full dose (44mg) Q1W thereafter in combination with either LEN (25mg) or POM (4mg) on Days 1 to 21 of a 28-day cycle. Dose-limiting toxicity (DLT) was monitored to the end of the first cycle. Treatment-emergent adverse events (TEAEs) were graded by Common Terminology Criteria for Adverse Events (v4.03), and cytokine release syndrome (CRS) by American Society for Transplantation and Cellular Therapy criteria. Pharmacokinetics, cytokine profiling, and T cell immunophenotyping were performed. Response was assessed by International Myeloma Working Group (IMWG) criteria. Minimal residual disease (MRD) was assessed by next generation sequencing at a sensitivity of 1×10 -5, in accordance with IMWG criteria.

Results: 58 pts received elranatamab SC as a single agent (n=50) or in combination with either LEN (n=4) or POM (n=4) as of 4-Feb-2021. Pts had a median (range) age of 64 (32-86) years, and 26% were Black/African American or Asian. Pts had a median of 6 prior regimens, 98% had triple-class relapsed/refractory disease, 45% had prior high-dose chemotherapy with stem cell transplantation, and 22% had prior BCMA-targeted therapy. The most common all causality TEAEs included CRS (n=48, 83%; none higher than G2), lymphopenia (n=37, 64%; 12% G3, 52% G4), neutropenia (n=37, 64%; 31% G3, 29% G4), anemia (n=32, 55%; 38% G3, 0% G4), injection site reaction (n=31, 53%; none higher than G2), and thrombocytopenia (n=30, 52%; 14% G3, 17% G4). At the RP2D of 1000μg/kg, median duration of CRS decreased by 50% from 4 days to 2 days with priming. Two of 58 pts had DLT including G4 thrombocytopenia (Part 1.1) and G4 neutropenia (POM). Exposure increased with dose, cytokine increases occurred with the first dose, and increased T-cell proliferation was observed in peripheral blood. Median duration of follow-up was 7.5, 2.3, and 1.9 months for the dose escalation, priming, and LEN/POM combination cohorts, respectively. For pts treated across the efficacious dose range (215-1000μg/kg) in Part 1, confirmed overall response rate (ORR) was 70% (14/20) with complete response (CR)/stringent CR (sCR) rate of 30% (6/20). For the 14 pts with confirmed responses, median duration of response had not yet been reached; the probability (95% CI) of responders being event free at 6 months was 92.3% (56.7-98.9). Confirmed ORR at the RP2D was 83% (5/6). Responses in this RRMM population included sCR (n=5), CR (n=1), very good partial response (VGPR; n=7), and partial response (n=1). Median time to response was 22 days. Importantly, 100% (4/4) of evaluable pts with baseline dominant sequence and on-treatment sample at CR/sCR achieved MRD negativity at 1×10 -5 by IMWG criteria, and 75% (3/4) of pts with prior BCMA-targeted therapy achieved response (1 sCR, 2 VGPR). Updated efficacy, safety, and MRD results will be presented for SC parts of the study.

Conclusions: Elranatamab as a single agent, administered either Q1W or Q2W, had a manageable safety profile for pts with RRMM. Across the efficacious dose range, elranatamab achieved confirmed ORR of 70% and CR/sCR rate of 30%, with confirmed ORR of 83% at the RP2D. Importantly, elranatamab induces deep and durable clinical responses in RRMM pts with and without prior BCMA-targeted therapy and 100% MRD negativity in MRD evaluable pts. These results, along with emerging combination data, support continued development of elranatamab as a single agent and in combination with standard therapies for MM.

Disclosures

Sebag: Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Research Funding; Bristol Myers-Squibb: Consultancy, Honoraria. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Bahlis: GlaxoSmithKline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Genentech: Consultancy; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Dholaria: Pfizer: Research Funding; Poseida: Research Funding; Angiocrine: Research Funding; MEI: Research Funding; Jazz: Speakers Bureau; Takeda: Research Funding; Janssen: Research Funding; Celgene: Speakers Bureau. Solh: Partner Therapeutics: Research Funding; Jazz Pharmaceuticals: Consultancy; BMS: Consultancy; ADCT Therapeutics: Consultancy, Research Funding. Levy: Bristol Myers Squibb: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Amgen Inc.: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Beigene: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences, Inc.: Consultancy, Honoraria, Speakers Bureau; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Morphosys: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Speakers Bureau; Dova: Consultancy, Other: Promotional speaker; Epizyme: Consultancy, Other: Promotional speaker; Novartis: Consultancy, Other: Promotional speaker; GSK: Consultancy, Other: Promotional speaker. Tomasson: Pfizer, Inc.: Research Funding; Rafael Pharmaceuticals: Research Funding; syros Pharmaceuticals: Research Funding; Janssen R&D: Research Funding; Seagen, Inc.: Research Funding. Dube: Pfizer: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Damore: Pfizer: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Lon: Pfizer: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Basu: Pfizer: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Skoura: Pfizer: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Chan: Pfizer: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Trudel: Amgen: Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Roche: Consultancy; Janssen: Honoraria, Research Funding; Sanofi: Honoraria; Pfizer: Honoraria, Research Funding; Genentech: Research Funding. Jakubowiak: Gracell: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Chu: Celgene/BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Teva: Consultancy, Honoraria. Gasparetto: Janssen: Consultancy; Sanofi: Consultancy, Honoraria, Speakers Bureau; Oncopeptide: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Speakers Bureau; Gsk: Consultancy, Honoraria, Speakers Bureau. Lesokhin: pfizer: Consultancy, Research Funding; Behringer Ingelheim: Honoraria; Trillium Therapeutics: Consultancy; bristol myers squibb: Research Funding; Genetech: Research Funding; Iteos: Consultancy; Janssen: Honoraria, Research Funding; Serametrix, Inc: Patents & Royalties.

© 2021 by The American Society of Hematology
2021
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