FDA Halts Pembrolizumab Trials in Multiple Myeloma

The FDA determined that the risks of treatment outweigh any potential benefit

The US Food and Drug Administration (FDA) placed a clinical hold on three trials of the PD-1 inhibitor pembrolizumab in combination with pomalidomide or lenalidomide for patients with multiple myeloma: KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.

The decision was based on data from the trials that showed more deaths in the pembrolizumab arms of KEYNOTE-183 and KEYNOTE-185. Patient enrollment into these trials was halted on June 12, and since then, the FDA determined that the available data indicated that the risks of treatment with pembrolizumab plus pomalidomide or lenalidomide outweigh any potential benefit.

The KEYNOTE-183 trial was a phase III trial studying pomalidomide and low-dose dexamethasone with or without pembrolizumab in refractory or relapsed multiple myeloma. KEYNOTE-185 was a phase III trial of lenalidomide and low-dose dexamethasone with or without pembrolizumab in newly diagnosed, treatment-naive myeloma.

KEYNOTE-023 was a phase I trial of pembrolizumab with backbone treatment for multiple myeloma. KEYNOTE-023 had been placed on a partial clinical hold.

According to Merck, the clinical hold does not apply to any other studies of pembrolizumab. A search of clinicaltrials.gov shows several trials of pembrolizumab are suspended; however, according to the site, several are still recruiting or active including trials looking at pembrolizumab/lenalidomide in post autologous stem cell transplant in high-risk disease, pembrolizumab in combination with NY-ESO-1^C259T, and acalabrutinib plus pembrolizumab to treat hematologic malignancies.

In addition, earlier this year, results of a phase II study of combination pembrolizumab, pomalidomide, and low-dose dexamethasone produced data supporting, “a synergistic activity between pomalidomide and pembrolizumab that led to high overall response rate (60%) that were remarkably durable” in patients with heavily pretreated myeloma.

The study, which was published in Blood, looked at the combination in 48 patients and showed that 60% of patients had an objective response to treatment. Four patients had a stringent response or complete response, nine patients had a very good partial response, and 16 patients had a partial response. The median duration of response was longer than 1 year. Patients with double-refractory disease had an overall response rate of 68%.