The Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee voted in favor (12-0) of the approval of belantamab mafodotin (GSK2857916; GlaxoSmithKline) for patients with relapsed or refractory multiple myeloma (RRMM) who have received at least 4 prior therapies including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.
Belantamab mafodotin is a humanized, afucosylated, IgG1 anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent, monomethyl auristatin F. The vote was based on data from the DREAMM clinical trial program, which included the pivotal, 2-arm, open-label phase 2 DREAMM-2 trial that assessed the efficacy and safety of belantamab mafodotin in 196 patients with relapsed or refractory multiple myeloma after 3 or more lines of therapy that included an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.
Patients were randomized to receive belantamab mafodotin 2.5mg/kg (n=97) or 3.4mg/kg (n=99) via intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. The primary end point was the overall response rate, defined as the proportion of patients with a confirmed partial response (PR) or better.
Findings showed that patients in the 2.5mg/kg and 3.4mg/kg cohorts achieved overall response rates (ORR) of 31% (97.5% CI, 20.8-42.6) and 34% (97.5% CI, 20.8-42.6), respectively, according to a published study in The Lancet Oncology. In meeting documents, the committee noted that the demonstrated ORR of 31% may be beneficial in heavily pretreated patients with RRMM.
With regard to safety, the most common grade 3-4 adverse events reported in the 2.5mg/kg and 3.4mg/kg cohorts were keratopathy (27% [n=26] and 21% [n=21]), thrombocytopenia (20% [n=19] and 33% [n=33]), and anemia (20% [n=19] and 25% [n=25]), respectively. The Company reported that a Risk Evaluation and Mitigation Strategy (REMS) would be implemented to ensure the benefits of the drug outweighed the risk of ocular toxicity (ie, keratopathy, decreases in visual acuity, including severe vision loss). However, the committee continued to express concerns over the potential for ocular toxicity, despite the dose modification strategy proposed by the Company to mitigate the risk.
“Although the efficacy results from DREAMM-2 suggest a benefit with belantamab mafodotin in the proposed population of patients with RRMM, it is not clear whether the benefit outweighs the risks of ocular toxicity,” the panel stated. They added that “given the high rates of corneal [adverse events] observed with the 2.5mg/kg Q3W dose, and the limited data available at lower doses or alternative regimens, additional clinical safety and efficacy information for belantamab mafodotin is needed to determine the optimal dose that will mitigate the risk of corneal toxicity without a clinically significant impact on efficacy.”
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval. The FDA previously granted Priority Review and Breakthrough Therapy designations to belantamab mafodotin for this indication.
For more information visit fda.gov.