FDA calls a partial halt to nivolumab trials in MM

According to an announcement by Reuters on September 6^th, 2017, the U.S. Food and Drug Administration (FDA) has called a partial halt to three clinical trials testing nivolumab in Multiple Myeloma (MM) patients, in combination with other medicines. Nivolumab is a human anti-PD-1 (programmed cell death – 1) receptor monoclonal antibody and belongs to the class of drugs known as checkpoint inhibitors. Blocking PD-1 removes the negative regulation of T-cell activation and response, thus exposing the tumor to immune attack.

The clinical trials affected are CheckMate-602, CheckMate-039 and CA204142. Patients already enrolled on the trials and showing beneficial responses will be allowed to continue, but no new participants will be recruited. Bristol Myers Squibb, who markets the drug, have said they are committed to working with the FDA to ensure that the best interests of MM patients are met.

This decision by the FDA was based on independent assessments of other trials for checkpoint inhibitors, which deemed the risk too great to outweigh potential benefits, and follows the hold put on two trials of Merck’s checkpoint inhibitor Keytruda® (pembrolizumab), in July – see previous MM Hub article.

This latest decision beckons further investigation into the mechanism of action of the PD-1/PD-L1 signaling axis in MM. Previous trials have shown that PD1 inhibition alone is not beneficial in MM, but data from early trials testing combination therapies have suggested it can add value to current regimens. The question going forward is whether the added value is worth the increased risk these drugs seem to pose.