FDA Slaps Partial Hold on 3 of Bristol-Myers Squibb's Opdivo-Based Combo Trials
September 7, 2017
By Mark Terry, BioSpace.com Breaking News Staff
In another case responding to risks associated with Merck ’s Keytruda (pembrolizumab), the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on three of Bristol-Myers Squibb ’s clinical trials of Opdivo (nivolumab) in patients with relapsed or refractory multiple myeloma.
BioSpace previously reported that the FDA had placed six of Celgene (CELG)’s clinical trials of its Imfinzi (durvalumab), an anti-PD-L1 antibody, in combination with other immune and chemotherapeutic drugs on partial or full clinical holds. This is based on issues with Merck’s KEYNOTE-183 and KEYNOTE-185 clinical trials. John Carroll, writing for Endpoints News, notes, “Those multiple myeloma trials matched Merck’s blockbuster therapy with two drugs from Celgene: Pomalyst and its big drug Revlimid. The FDA also ordered patients taken off of treatment in KEYNOTE-023 Cohort 1, matching Keytruda in combination with lenalidomide and dexamethasone in patients who received prior anti-multiple myeloma treatment with an immunomodulatory (IMiD) treatment (lenalidomide, pomalidomide or thalidomide).”
The clinical trials placed on partial hold for Bristol-Myers Squibb are:
• CheckMate-602: A Phase III trial of nivolumab, elotuzumab, pomalidomide and dexamethasone in relapsed and refractory multiple myeloma (MM).
• CheckMate-039: A Phase I trial of nivolumab and the combination of nivolumab and daratumumab, with or without pomalidomide and dexamethasone in patients with relapsed or refractory MM.
• CA204142: A Phase I trial of elotuzumab in combination with pomalidomide and low-dose dexamethasone, and in combination with nivolumab, in patients with MM relapsed or refractory to prior treatment with lenalidomide.
Patients currently enrolled in these trials who are seeing clinical benefit can continue treatment. No new patients will be enrolled at this time.
Bristol-Myers indicates that its other studies of Opdivo for other indications besides MM will continue as planned.
Carroll writes, “Combined, these companies [Celgene and Bristol-Myers Squibb] have hundreds of combo studies underway, but regulators clearly believe that there’s some other threat to patients in these particular combination studies using Celgene’s mainstay therapies. The FDA highlighted that concern just a week ago, carefully spelling out their reasons for suspending the three Merck studies and pointing out they were hunting down and reviewing other, similar PD-(L)1 combos in the clinic.”
On August 31, the FDA posted an alert about Merck’s Keytruda in combination with dexamethasone and lenalidomide or pomalidomide in patients with MM. “The FDA statement is based on review of data from two clinical trials (KEYNOTE-183 and KEYNOTE-185) evaluating the use of Keytruda (pembrolizumab) combined with other treatments in patients with multiple myeloma. On July 3, 2017, the FDA required that all patients in these trials be discontinued from further investigation with this drug, because interim results from both trials demonstrated an increased risk of death for patients receiving Keytruda (pembrolizumab) when it was combined with an immunomodulatory agent as compared to the control group.”
On Tuesday, the Cellectis reported the death of the first patient to receive its CAR-T product. Juno Therapeutics reported three patients deaths in one of its own CAR-T products last year, eventually forcing it to shutter one of its programs.
All of which underlines that cutting-edge immuno-oncology therapies, as dazzling as they often are, are also risky new treatments. Carroll writes, “Clearly, though, as researchers continue to test the boundaries of what these new therapies can do unexpected safety issues continue to arise, raising questions of just how far developers should take the drugs….At this point, regulators appear to be shifting their position from an encouraging signal to floor it, to a more cautious position of studying safety threats before barreling ahead.”