The FDA has placed 3 clinical trials of Keytruda (pembrolizumab) on hold in response to a pattern of patient deaths, according to a statement from Merck
, the immuno-oncology drug’s manufacturer.
Pembrolizumab has already been approved by the FDA for treating certain types of cancers, like relapsed/refractory Hodgkin lymphoma, but the 3 interrupted studies were assessing its use in patients with various types of multiple myeloma. All were combination studies; 2 phase III studies (KEYNOTE-183, KEYNOTE-185) were placed on full clinical hold while the phase I study (KEYNOTE-023) was placed on partial hold, meaning just 1 cohort will stop participating in the trial.
KEYNOTE-183 studied pembrolizumab in combination with pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.
KEYNOTE-185 studied pembrolizumab in combination with lenalidomide and low-dose dexamethasone in those with newly diagnosed and treatment naïve multiple myeloma.
KEYNOTE-023 studied pembrolizumab in combination with various backbone treatments. The cohort that must discontinue treatment was Cohort 1, which combined pembrolizumab with lenalidomide and dexamethasone for patients who had already been treated for multiple myeloma with an immunomodulatory treatment.
According to Merck, the FDA’s decision to suspend the trials and order participants to discontinue use of the drug resulted from the Data Monitoring Committee’s observation of more deaths in the study groups taking pembrolizumab in these trials and its subsequent determination that the risks of taking the drug outweighed any potential benefits. The decision to place the trials on hold occurred less than 3 weeks after the FDA recommended pausing the enrollment
of new patients in the phase III studies in order to more closely analyze the participants’ deaths.
“Patient safety is Merck’s primary concern, and we are grateful to the study investigators and patients involved in these studies for their commitment to this important research,” said Roger M. Perlmutter, MD, PhD, president of Merck Research Laboratories, in the press statement. “Merck’s development program for KEYTRUDA, spanning more than 30 different tumor types, has one priority: helping patients suffering from cancer.”
Other trials in the KEYNOTE program will continue to test the programmed death-1 inhibitor in patients with other cancers. In May 2017, the FDA granted pembrolizumab accelerated approval
for treating cancers with certain tumor characteristics—unresectable or metastatic microsatellite instability-high or mismatch repair deficient solid tumors—in patients without suitable alternative treatments. It marked the first time the agency had granted an indication for a cancer therapy based on a biomarker instead of where in the body the tumor began.