Following Pembrolizumab, Nivolumab Trials in Multiple Myeloma Paused

In a press release late Wednesday, Bristol-Myers Squibb (BMS) announced that the FDA has placed a clinical hold on 3 combination trials evaluating its programmed death-1 (PD-1) inhibitor nivolumab (Opdivo) in patients with relapsed/refractory multiple myeloma.

The hold, according to the company, is in reaction to trials evaluating another anti—PD-1 agent, pembrolizumab (Keytruda), that were placed on hold following patient deaths. In July, Merck, which has developed pembrolizumab, announced that the FDA’s decision applied to KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023; the trials were evaluating the drug in combination with various other agents in either treatment-naïve or relapsed/refractory patients with multiple myeloma.

Earlier this week, the FDA followed up with a more detailed analysis of what resulted in the deaths—higher rate of grade 3 to 5 toxicities, higher rate of serious adverse events, and some non-cancer causes of death, including cardiac events and intestinal ischemia.

Nivolumab trials that have been placed on partial clinical hold include:

• CheckMate-602: A phase 3 trial of combinations of nivolumab, elotuzumab, pomalidomide, and dexamethasone in relapsed and refractory multiple myeloma
• CheckMate-039: A phase 1 study to establish the tolerability of nivolumab and the combination of nivolumab and daratumumab, with or without IMiD (pomalidomide and dexamethasone), in subjects with relapsed or refractory multiple myeloma
• CA204142: A phase 2 study of elotuzumab in combination with pomalidomide and low-dose dexamethasone, and in combination with nivolumab, in patients with multiple myeloma relapsed or refractory to prior treatment with lenalidomide

Other nivolumab studies for indications other than multiple myeloma will continue as planned, according to the BMS release.