Targeting BCMA with the antibody–drug conjugate GSK2857916 is well tolerated in a phase I trial.
Major finding: Targeting BCMA with the antibody–drug conjugate GSK2857916 is well tolerated in a phase I trial.
Clinical relevance: At the recommended phase II dose, GSK2857916 achieves responses in 21 of 35 patients.
Impact: GSK2857916 may be safe and effective in patients with relapsed or refractory multiple myeloma.
Treatment options are limited for patients with relapsed or refractory multiple myeloma, and new therapies are needed to improve outcomes. The B-cell maturation antigen (BCMA) has emerged as a potential therapeutic target. BCMA is expressed on late-stage B cells and malignant plasma cells, and inhibition of BCMA suppresses multiple myeloma cell growth and survival. GSK2857916, a humanized BCMA antibody conjugated to the tubulin polymerization inhibitor monomethylauristatin F (MMAF), exhibited activity against multiple myeloma cells and primary samples. Based on these preclinical findings, Trudel and colleagues evaluated the safety and efficacy of GSK2857916 in a first-in-human open-label phase I dose escalation and expansion study in 73 heavily pretreated patients with relapsed or refractory multiple myeloma, 38 patients in the dose-escalation phase and 35 patients in the dose-expansion phase. The primary endpoints were maximum tolerated dose and recommended phase II dose, and secondary endpoints included preliminary antitumor activity. In the dose-escalation phase there were no dose-limiting toxicities, and GSK2857916 was well tolerated at the determined recommended phase II dose. Overall, there were 12 treatment-related serious adverse events. Corneal events occurred in 57.5% of patients, most of which were grade 1–2. At the recommended phase II dose, 21 of 35 patients (60%) achieved a response, including 3 complete responses, 15 very good partial responses, and 3 partial responses. Responses were durable, with a median progression-free survival of 7.9 months. Taken together, the results of this phase I trial indicate that GSK2857916 is well tolerated and has preliminary antitumor activity in patients with relapsed or refractory multiple myeloma.
Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, et al. Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol 2018;19:1641–53.
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