MAGNETISMM-1: PHASE 1 STUDY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) TARGETED CD3-ENGAGING BISPECIFIC ANTIBODY, FOR PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (MM)
Author(s): ,
Caitlin Costello
Affiliations:
Moores Cancer Center, University of California San Diego,La Jolla,United States
,
Noopur Raje
Affiliations:
Massachusetts General Hospital Cancer Center, Harvard Medical School,Boston,United States
,
Nizar Bahlis
Affiliations:
Arnie Charbonneau Cancer Institute, University of Calgary,Calgary,Canada
,
Bhagirathbhai Dholaria
Affiliations:
Vanderbilt-Ingram Cancer Center,Nashville,United States
,
Melhem Solh
Affiliations:
Blood and Marrow Transplant Group of Georgia, Northside Hospital,Atlanta,United States
,
Moshe Levy
Affiliations:
Department of Medical Oncology, Baylor Scott and White Health,Dallas,United States
,
Michael Tomasson
Affiliations:
Holden Comprehensive Cancer Center, University of Iowa,Iowa City,United States
,
Harman Dube
Affiliations:
Oncology Research and Development, Pfizer,San Diego,United States
,
Michael Damore
Affiliations:
Oncology Research and Development, Pfizer,San Diego,United States
,
Ken Liao
Affiliations:
Oncology Research and Development, Pfizer,San Diego,United States
,
Cynthia Basu
Affiliations:
Early Clinical Development, Pfizer,San Diego,United States
,
Athanasia Skoura
Affiliations:
Oncology Research and Development, Pfizer,Pennsylvania,United States
,
Edward Chan
Affiliations:
Oncology Research and Development, Pfizer,South San Francisco,United States
,
Suzanne Trudel
Affiliations:
Princess Margaret Cancer Centre, University Health Network,Toronto,Canada
,
Andrzej Jakubowiak
Affiliations:
Department of Medicine, University of Chicago Medical Center,Chicago,United States
,
Michael Chu
Affiliations:
Cross Cancer Institute,Edmonton,Canada
,
Cristina Gasparetto
Affiliations:
Department of Medicine, Duke University Cancer Institute,Durham,United States
,
Andrew Dalovisio
Affiliations:
Department of Hematology and Oncology, Ochsner Health,Jefferson,United States
,
Michael Sebag
Affiliations:
Cedars Cancer Center, McGill University Health Center,Montreal,Canada
Alexander Lesokhin
Affiliations:
Division of Hematology and Oncology, Memorial Sloan Kettering Cancer Center/Weill Cornell Medical College,New York,United States
EHA Library. Costello C. 06/09/21; 324600; S192
Caitlin Costello
Caitlin Costello
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S192

Type: Oral Presentation

Session title: T cell re-directing therapies in relapsed/refractory multiple myeloma

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. MagnetisMM-1 (ClinicalTrials.gov ID: NCT03269136) is a Phase 1 study of elranatamab designed to evaluate selective therapeutic targeting and activation of T cells re-directed against BCMA-expressing malignant plasma cells.

Aims
The aim of MagnetisMM-1 is to characterize the efficacy, safety, pharmacokinetics, and pharmacodynamics of elranatamab as a single agent and in combination with immunomodulatory agents for patients with relapsed or refractory MM.

Methods
Patients (pts) received single agent elranatamab at 80, 130, 215, 360, 600, and 1000μg/kg/week subcutaneously (SC). 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). The recommended Phase 2 dose for single agent elranatamab is 1000 μg/kg SC weekly. Updated data, including duration of response, will be presented.

Conclusion
Elranatamab demonstrated a manageable safety profile and wide therapeutic index.  Doses ≥215μg/kg SC achieved ORR of 75% with CR/sCR rate of 30%. These results demonstrate the safety and efficacy of elranatamab in this relapsed/refractory population, confirm the feasibility and potential of BCMA-directed immunotherapy for malignant plasma cell disorders, and support ongoing development of elranatamab for pts with MM.

Keyword(s): Immunotherapy, Multiple myeloma

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S192

Type: Oral Presentation

Session title: T cell re-directing therapies in relapsed/refractory multiple myeloma

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. MagnetisMM-1 (ClinicalTrials.gov ID: NCT03269136) is a Phase 1 study of elranatamab designed to evaluate selective therapeutic targeting and activation of T cells re-directed against BCMA-expressing malignant plasma cells.

Aims
The aim of MagnetisMM-1 is to characterize the efficacy, safety, pharmacokinetics, and pharmacodynamics of elranatamab as a single agent and in combination with immunomodulatory agents for patients with relapsed or refractory MM.

Methods
Patients (pts) received single agent elranatamab at 80, 130, 215, 360, 600, and 1000μg/kg/week subcutaneously (SC). 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). The recommended Phase 2 dose for single agent elranatamab is 1000 μg/kg SC weekly. Updated data, including duration of response, will be presented.

Conclusion
Elranatamab demonstrated a manageable safety profile and wide therapeutic index.  Doses ≥215μg/kg SC achieved ORR of 75% with CR/sCR rate of 30%. These results demonstrate the safety and efficacy of elranatamab in this relapsed/refractory population, confirm the feasibility and potential of BCMA-directed immunotherapy for malignant plasma cell disorders, and support ongoing development of elranatamab for pts with MM.

Keyword(s): Immunotherapy, Multiple myeloma

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