The BCMA-targeting humanized bispecific monoclonal antibody elranatamab (PF-06863135) elicited high response rates when subcutaneously delivered at higher doses in patients with relapsed/refractory multiple myeloma, according to data from a phase 1 clinical trial (NCT03269136) presented during the 2021 ASCO Annual Meeting.

About Elranatamab

Bispecific antibody constructs represent an innovative immunotherapy approach that helps the body’s immune system target cancer cells and appears very promising for the treatment of multiple myeloma. Bispecific antibodies are antibodies with two arms. One arm of the drug attaches to a specific protein on the cancer cell. The other arm activates immune cells in the patient to kill the cancer cells. Elranatamab is a BCMA x CD3 bispecific antibody designed to bind to BCMA on multiple myeloma cells and the CD3 receptor on T-cells, bridging them together and activating T-cell killing of the cancerous myeloma cells.

The current clinical trial was designed to assess the safety tolerability of elranatamab and determine the optimal dose for additional study. Dose ranging occurred in 30 patients who on average had received 8 prior treatments. The majority (87%) had triple-refractory disease, with nearly all patients (97%) having received prior anti-CD38 therapy. Twenty-three percent of patients received BCMA-directed antibody drug conjugate or chimeric antigen receptor (CAR) T-cell therapy.

Patients responded to treatment at all dose levels and there was a dose response effect – higher doses yielded more responses than lower doses. Within the entire study population, the most common side effects were lymphopenia, low grade cytokine release syndrome, anemia, thrombocytopenia, and neutropenia. No dose-limiting toxicities were identified.

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Elranatamab was well tolerated and demonstrated significant anti-myeloma activity and will continue development both as monotherapy or in combination with other anti-myeloma drugs.

Reference

Bahlis NJ, Raje NS, Costello C, et al. 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). Presented at: 2021 ASCO Annual Meeting. June 4-8, 2021. Virtual.