FDA Allows Trials of Opdivo Combo Therapy to Resume, Signaling No New Safety Concerns

FDA Allows Trials of Opdivo Combo Therapy to Resume, Signaling No New Safety Concerns

The U.S. Food and Drug Administration (FDA) agreed to allow two clinical trials of Opdivo (nivolumab)-based combinations for myeloma to resume, after being put on partial hold in September 2017, the treatments developer, Bristol-Myers Squibb, announced.

Safety issues detected in clinical trials of similar Keytruda (pembrolizumab)-based combinations prompted the FDA to suspend several trials of other checkpoint inhibitors tested with immunomodulatory drugs.

Bristol-Myers Squibb consulted with the regulatory agency and modified its study protocol to allow continuing recruitment, it stated in a press release.

The two affected trials — the Phase 1 CheckMate -039 (NCT01592370) and a Phase 2 (NCT02612779) study — both explore Opdivo-based combinations in patients with relapsed or refractory multiple myeloma.

Patients already in these studies were allowed continue treatment if their physicians deemed it beneficial, but the studies were prevented from recruiting more patients.

In the Phase 1 study, Opdivo and Darzalex (daratumumab) is given to relapsed or refractory myeloma patients, some of whom are already using Pomalyst (pomalidomide) and dexamethasone.

The Phase 2 trial explores a combination of Opdivo and Empliciti (elotuzumab), or Empliciti, Pomalyst, and dexamethasone.

A third study — a Phase 3 trial (NCT02726581) exploring Opdivo, Empliciti, Pomalyst, and dexamethasone in relapsed or refractory myeloma patients — remains on a partial hold while Bristol-Myers Squibb discusses with the FDA how to proceed. Patients in this trial who are showing benefit are also continuing on treatment, but no new patients are being enrolled, the release said.

In June 2016, Merck detected unexplained deaths among myeloma patients being treated with a combination of Keytruda and immunomodulatory drugs, including Pomalyst and Revlimid.

When notified of the safety risk, the FDA acted to shut down one Keytruda trial and place several others on partial hold.

But the agency soon announced that additional checkpoint inhibitors, targeting PD-1 or PD-L1, may be affected by these safety concerns if used with other with immunomodulatory and anti-cancer therapies for myeloma.

The Opdivo studies were the first to be placed on hold, allowing researchers to take a closer look at the data to detect any potential hazards. Later, AstraZeneca‘s trials of Imfinzi (durvalumab), used in combination with immunomodulatory and anti-cancer treatments for multiple myeloma, were also halted.

The Opdivo studies’ reopening signal that no new safety issues were detected. However, Bristol-Myers did not provide details on how the study protocols have been amended.

At this time, the affected Keytruda trials remain on hold.

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