The FDA has released a statement regarding safety concerns that led to a clinical hold on three trials of pembrolizumab in combination with pomalidomide or lenalidomide for patients with multiple myeloma, and the active role of the FDA in protecting patient safety.
In July, the US Food and Drug Administration (FDA) placed a clinical hold on three trials of the programmed death 1 (PD-1) inhibitor pembrolizumab in combination with pomalidomide or lenalidomide for patients with multiple myeloma: KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.
The hold was announced based on data from these trials that showed more deaths on the pembrolizumab arms of KEYNOTE-183 and KEYNOTE-185, indicating that the risks of treatment with the investigational drug plus pomalidomide or lenalidomide outweighed any potential benefit.
Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, recently released a statement regarding these safety concerns and the active role of the FDA in protecting patient safety.
“While much effort is put into early research to ensure that no major safety issues exist before therapies are tested in patients, these trials are ultimately designed to provide vital information about the safety and efficacy of the treatments in people, so the FDA can help ensure that the benefits to the intended patients outweigh the risks,” she wrote in the statement.
The FDA is actively examining data from the pembrolizumab trials and working with the drug’s manufacturer, Merck, to better understand the cause of the safety concerns. In addition, the FDA has begun work with other sponsors of clinical trials of PD-1 and programmed death ligand 1 (PD-L1) inhibitors, where they are being tested with immunomodulatory agents.
“The FDA will take appropriate action as warranted to ensure patients enrolled in these trials are protected and that doctors and clinical trial researchers understand the risks associated with this investigational use,” Woodcock wrote.
The FDA is communicating with clinicians and patients to remind them that pembrolizumab is not approved and should not be given to patients in combination with immunomodulatory agents for the treatment of multiple myeloma.
“We also want to ensure that patients taking Keytruda and other PD-1/PD-L1 inhibitors know that the FDA still believes the benefits of taking these drugs for their approved uses and as indicated in the labels continue to outweigh their risks,” Woodcock wrote. “Patients taking these drugs for their approved uses should continue to take their medication as directed by their healthcare professional.”
The clinical hold put on KEYNOTE-183 and -185 does not apply to any other studies of pembrolizumab, including several that are still recruiting or active.