Efficacy and safety of elranatamab (PF-06863135), a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MM).

Authors

null

Nizar J. Bahlis

Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada

Nizar J. Bahlis , Noopur S. Raje , Caitlin Costello , Bhagirathbhai R. Dholaria , Melhem M. Solh , Moshe Y. Levy , Michael H Tomasson , Harman Dube , Feng Liu , Kai Hsin Liao , Cynthia Basu , Athanasia Skoura , Edward Michael Chan , Suzanne Trudel , Andrzej J. Jakubowiak , Michael P Chu , Cristina Gasparetto , Andrew Dalovisio , Michael Sebag , Alexander M. Lesokhin

Organizations

Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada, Massachusetts General Hospital, Harvard Medical School, Boston, MA, Moores Cancer Center, University of California San Diego, La Jolla, CA, Vanderbilt-Ingram Cancer Center, Nashville, TN, Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA, Department of Medical Oncology, Baylor Scott and White Health, Dallas, TX, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, Oncology Research and Development, Pfizer, San Diego, CA, Early Clinical Development, Pfizer, San Diego, CA, Oncology Research and Development, Pfizer, Pennsylvania, PA, Oncology Research and Development, Pfizer, South San Francisco, CA, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, Department of Medicine, University of Chicago Medical Center, Chicago, IL, Cross Cancer Institute, Edmonton, AB, Canada, Department of Medicine, Duke University Cancer Institute, Durham, NC, Department of Hematology and Oncology, Ochsner Health, Jefferson, LA, Cedars Cancer Center, McGill University Health Center, Montreal, QC, Canada, Division of Hematology and Oncology, Memorial Sloan Kettering Cancer Center/Weill Cornell Medical College, New York, NY

Research Funding

Pharmaceutical/Biotech Company
Pfizer

Background: Elranatamab (PF-06863135) is a humanized bispecific monoclonal antibody (IgG2a) that targets BCMA, a member of the tumor necrosis factor receptor superfamily expressed in MM, and CD3 on T cells. We reported results for intravenous (IV) dosing (Raje et al. Blood. 2019;134(S1):1869) and now update for subcutaneous (SC) dosing from the ongoing Phase 1 study (MagnetisMM-1). Methods: Patients (pts) received elranatamab at 80, 130, 215, 360, 600, and 1000μg/kg SC weekly. A modified toxicity probability interval method was used for escalation, with monitoring for dose-limiting toxicity (DLT) to 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 (Lee et al. Biol Blood Marrow Transplant. 2019;25:625). Response was assessed by International Myeloma Working Group criteria. Pharmacokinetics, cytokine profiling, and T cell immunophenotyping were performed. Results: 30 pts had received elranatamab as of 4-Aug-2020 at 80 (n = 6), 130 (n = 4), 215 (n = 4), 360 (n = 4), 600 (n = 6), or 1000 (n = 6) μg/kg SC weekly. Pts had a median of 8 prior treatments; 87% had triple refractory disease, 97% had prior anti-CD38 therapy, and 23% had prior BCMA-directed antibody drug conjugate or chimeric antigen receptor T cell therapy. The most common all causality TEAEs included lymphopenia (n = 24, 80%; 20% G3, 60% G4), CRS (n = 22, 73%; none > G2), anemia (n = 17, 57%; 43% G3, 3% G4), injection site reaction (n = 16, 53%; none > G2), thrombocytopenia (n = 16, 53%; 23% G3, 17% G4), and neutropenia (n = 12, 40%; 17% G3, 17% G4). Both CRS and immune effector cell-associated neurotoxicity syndrome (n = 6, 20%) were limited to ≤G2 with median durations of 2 and 1.5 days, respectively. No DLT was observed. Exposure increased with dose, and Tmax ranged from 3–7 days. Cytokine increases occurred with the first dose, and increased T-cell proliferation was observed in peripheral blood. The overall response rate (ORR) for doses ≥215μg/kg was 75% (n = 15/20) including partial response (PR; n = 6), very good PR (VGPR; n = 3), complete response (CR; n = 1), and stringent CR (sCR; n = 5). Median time to response was 22 days, and 3 of 4 pts (75%) with prior BCMA-directed therapy achieved response (VGPR, n = 2 and sCR, n = 1). Updated data, including duration of response, will be presented. Conclusions: Elranatamab demonstrated a manageable safety profile, and SC doses ≥215μg/kg achieved ORR of 75% with CR/sCR rate of 30%. These results demonstrate the safety and efficacy of SC elranatamab in this relapsed/refractory population and support ongoing development of elranatamab for pts with MM, both as monotherapy and in combination with standard or novel therapies. Clinical trial information: NCT03269136

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Hematologic Malignancies—Plasma Cell Dyscrasia

Track

Hematologic Malignancies

Sub Track

Multiple Myeloma

Clinical Trial Registration Number

NCT03269136

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 8006)

DOI

10.1200/JCO.2021.39.15_suppl.8006

Abstract #

8006

Abstract Disclosures