External monitors press pause on KEYNOTE phase III clinical trials of Keytruda® (pembrolizumab)

Much emphasis has been put on immune checkpoint inhibitors as the rising stars in targeted therapy for Multiple Myeloma (MM). Keytruda® (pembrolizumab) is one such inhibitor targeting the programmed cell death receptor (PD-1) on lymphocytes, and was a major player in Merck’s portfolio, showing promising results in initial combination trials.

Yesterday an external data monitoring committee put the brakes on two phase III trials, KEYNOTE-183 and KEYNOTE-185, designed to assess the efficacy of pembrolizumab with pomalidomide and low-dose dexamethasone, and lenalidomide and low-dose dexamethasone, respectively. KEYNOTE-183 had enrolled heavily pre-treated MM patients that had received a minimum of two lines of prior treatment and were ineligible for transplant, whereas KEYNOTE-185 had enrolled patients with newly diagnosed MM who were treatment naive.

Patients currently enrolled in the trials will continue as planned, but researchers are no longer allowed to recruit new patients while an investigation is carried out. This decision was taken as a consequence of a higher than expected number of deaths. This will be a big setback for Merck, as a planned expansion of the treatment indication for pembrolizumab into MM would have been resting on these trials. Pembrolizumb is currently approved by both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of a number of other cancers, such as melanoma, advanced non-small lung cancer and Hodgkin’s Lymphoma; and by the FDA for the treatment of bladder cancer.