FDA places two combo studies of Roche's Tecentriq on partial hold
- Swiss pharma Roche said Friday the Food and Drug Administration put two early-stage combination studies involving its immunotherapy Tecentriq on partial clinical hold as part of a broader look into the safety of combining PD-(L)1 inhibitors with other immunomodulatory medicines in certain blood cancers.
- The two studies are investigating Tecentriq with either Celgene Corp.'s Revlimid or Pomalyst as a treatment for relapsed/refractory forms of multiple myeloma and follicular lymphoma. Under the partial hold, no additional patients can be enrolled.
- Other studies involving PD-(L)1 inhibitors from Merck & Co., Bristol-Myers Squibb Co. and AstraZeneca plc have also been put on clinical holds by the FDA after reports of patient deaths in two studies of Merck's Keytruda in multiple myeloma.
The clinical hold on the Roche study is just one of several placed on combination trials of PD-1/PD-L1 inhibitors with immunomodulatory drugs in multiple myeloma, raising concerns about the approach to treatment in hematological cancers.
"It is our understanding that the FDA is evaluating all ongoing blood cancer trials investigating an anti-PD1/PDL1 medicine in combination with an immunomodulatory medicine to determine if it is a class-wide (anti-PD1/PDL1) concern in multiple myeloma/blood cancers or a specific concern with certain combinations with immunomodulatory medicines," said Roche in its statement.
The concerns follow reports of patient deaths in two combination clinical trials of Merck & Co.'s Keytruda (pembrolizumab) with Pomalyst (pomalidomide) or Revlimid (lenalidomide), spurring the company to voluntarily pause recruitment in the KEYNOTE-183 and KEYNOTE-185 studies.
The FDA then placed both studies on full clinical hold and added a partial clinical hold for a third trial, KEYNOTE-023. The FDA also took the somewhat unusual step of putting out a statement at the end of August about the holds, stating that it "is actively examining the data from the Keytruda trials and working directly with Merck to better understand the true cause of the safety concerns."
The statement, made by the Center for Drug Evaluation and Research Director Janet Woodcock, also said that the agency would be working with sponsors of other PD-1/PD-L1 inhibitors to look at combinations with immunomodulatory agents in hematologic malignancies, and that the FDA would take "appropriate action as warranted" to protect patients.
As a result, there have been holds placed on combinations of AstraZeneca's Imfinzi (durvalumab) and a number of Celgene's immunomodulatory agents, and combinations of Bristol-Myers Squibb's Opdivo (nivolumab) and a variety of different immunomodulators.
- Roche Statement
- BioPharma Dive New PD-1 clinical holds raise more concerns for class
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