The partial hold that was placed on two clinical trials to assess Opdivo® (nivolumab) in combination regimens treating Relapsed and Refractory Multiple Myeloma (RRMM) patients, has now been lifted by the US Food and Drug Administration (FDA). The announcement was made by Bristol-Myers Squibb (BMS) on Tuesday 5th December 2017.
The decision by the FDA to pause the trials was made in September 2017 – see previous MM Hub article, and came in the wake of a number of unexplained deaths in other trials testing similar agents known as checkpoint inhibitors (pembrolizumab and atezolizumab). Nivolumab is a human monoclonal antibody targeting the programmed cell death-1 (PD-1) receptor and acts to remove negative regulation of T-cells, thereby activating natural tumor immune defense mechanisms.
Two of the nivolumab trials will now resume with amends to the original study protocols: CheckMate-039, a phase I trial of nivolumab and daratumumab, with or without IMiD (pomalidomide and dexamethasone) and CA204142, a phase II trial of nivolumab and elotuzumab with pomalidomide and low-dose dexamethasone. The third trial (CA209 or CheckMate-602) remains on partial clinical hold with enrolment suspended but patients allowed to continue treatment if showing signs of response.
Opdivo represents a huge slice of the BMS immuno-oncology portfolio and is already licensed for the treatment of other cancers including several solid tumors and classical Hodgkin Lymphoma (cHL). Therefore, plans to expand the indication of nivolumab to that of to that of hematological malignancies was a large part of its clinical development program, and BMS is therefore committed to working with the FDA in order to move forward with plans as originally set out.