FDA cautiously lifts holds on combo studies of checkpoint inhibitors
- The Food and Drug Administration has permitted several combination studies testing checkpoint inhibitors together with immunomodulatory drugs in multiple myeloma to resume enrollment, lifting partial clinical holds placed on trials conducted by Bristol-Myers Squibb Co. and the Swiss pharma Roche.
- In September, the agency directed Bristol-Myers, Roche and AstraZeneca plc to pause patient recruitment into their respective combo studies as it investigated whether pairing PD-1/L1 inhibitors with drugs like Celgene Corp.'s Revlimid or Pomalyst posed a safety risk.
- Concerns about the combinations were initially triggered by interim data from two studies evaluating Merck & Co.'s Keytruda together with Revlimid and Pomalyst that showed a higher number of deaths in the Keytruda groups. Those two plus another study were eventually put on full or partial holds.
The green light from the FDA for Bristol-Myers and Roche to proceed with patient enrollment eases some of the concerns initially prompted by the September holds. That the agency was comfortable with allowing trial resumption suggests that a review of evidence from the studies did not point to a broader class-wide safety risk.
No unexpected safety signals had been observed in the studies conducted by Bristol-Myers, AstraZeneca or Roche. Rather, the FDA appeared to be moving cautiously following the patient deaths observed in the Merck trials.
In a Dec. 5 statement, Bristol-Myers said the FDA had cleared two trials, CHECKMATE-039 and CA204142, to resume patient enrollment. The first study, currently in Phase 1, tests Opdivo (nivolumab) and Johnson & Johnson's Darzalex (daratumumab) with or without Pomalyst (pomalidomide) plus chemotherapy in relapsed or refractory multiple myeloma.
CA204142, on the other hand, is evaluating Bristol-Myers' Empliciti (elotuzumab) paired with either Pomalyst or Opdivo in patients with multiple myeloma following treatment with Revlimid (lenalidomide).
But the FDA is not sounding a full all-clear just yet.
Recruitment into a third study, which pairs Opdivo with either Empliciti or Pomalyst plus dexamethasone, remains halted, although patients who experience benefit from treatment can continue dosing.Bristol-Myers said it continues to work with the FDA to determine next steps for that trial.
A spokesperson for Merck confirmed that the full or partial holds placed on its three studies in July remain in place. AstraZeneca did not respond to BioPharma Dive's inquiries regarding its clinical trials by time of publication.
For Roche, the FDA agreed to lift its partial clinical holds on two studies of Tecentriq together with immunomodulatory drugs in multiple myeloma and follicular lymphoma. Both of the studies will proceed as planned, the Swiss pharma said.
Editor's note: This article has been updated to reflect a comment provided to BioPharma Dive by a spokesperson for Merck & Co. after publication.
- Bristol-Myers Squibb Co. Statement
- BioPharma Dive New PD-1 clinical holds raise more concerns for class
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