Following the halt called by an external data monitoring committee to two phase 3 trials testing pembrolizumab (Keytruda) in patients with MM (as previously reported on the MM Hub), the FDA has now called a complete stop to both studies. The trials were designed to assess the benefit of pembrolizumab in combination with the backbone regimens of dexamethasone and pomalidomide, and lenalidomide and dexamethasone, KEYNOTE-183 and KEYNOTE-185 trials, respectively.
This follows an investigation into a higher than average number of deaths in the test patient population, and the decision was made by the external committee to refuse any further recruits to the trials, although patients already taking pembrolizumab could continue. However, the US Food and Drug Administration (FDA) has now called a complete stop, asking for patients to be taken off pembrolizumab altogether. No further information has been revealed about the exact cause of the deaths, although it has been postulated that lung infections, noted as a side-effect in other trials with pembrolizumab, may be to blame. It appears that an additional phase I study was also put on hold.
Pembrolizumab is a monoclonal antibody and a member of the family of therapies called checkpoint inhibitors, which block proteins involved in immune suppression of cancer cells. Pembrolizumab has been much discussed in reference to MM at recent congresses and was heralded a success after several earlier trials indicated durable responses. This will, therefore, be a severe disappointment for Merck, who already market the drug for use in several other cancers and had hoped to extend the indication to MM. However, the FDA has stated that currently, the benefits do not appear to outweigh the potential risk to patients.