Safety Concerns Lead to Partial Hold of 2 Tecentriq Trials in Myeloma, Lymphoma

Based on recently published safety data, two clinical trials evaluating combinations of Tecentriq (atezolizumab) in multiple myeloma and follicular lymphoma patients were placed on partial clinical hold at the request of the U.S. Food and Drug Administration (FDA).

Unexplained deaths in trials of Keytruda-based combinations prompted the FDA to halt other studies of immune checkpoint inhibitors targeting the PD-1 or PD-L1 proteins in combination with other drugs. There have been no reports of safety concerns in the Tecentriq trials.

Patients in the Tecentriq trials can continue taking their combination treatments if researchers believe they are benefiting from them, but the trials will stop recruiting additional participants until the hold is lifted.

The two studies, conducted by Roche, were both evaluating Tecentriq in combination with immunomodulatory drugs.

The Phase 1b trial (NCT02431208) was studying Tecentriq plus Darzalex (daratumumab) with or without the immunomodulatory agents Revlimid (lenalidomide) or Pomalyst (pomalidomide) in patients with relapsed or refractory multiple myeloma. Some patients also received Tecentric alone or in combination with Revlimid.

The Phase 1b/2 study (NCT02631577) was studying the safety and efficacy of Tecentriq in combination with Gazyva (obinutuzumab) plus Revlimid (lenalidomide) in patients with relapsed or refractory follicular lymphoma.

Tecentriq, currently owned by Genentech, is an immunotherapy designed to bind the PD-L1 protein, which plays a role in preventing the body’s immune system from fighting cancer. By binding to PD-L1, the drug removes the “stop sign” and activates the immune response.

The FDA’s concern about Tecentriq started when Merck reported unexplained deaths among patients treated with a combination of Keytruda (pembrolizumab) and immunomodulatory drugs, including Pomalyst and Revlimid.

This prompted the agency to shut down one Keytruda trial and place several others on partial hold in July 2017.

But while the safety concerns were seen in Keytruda trials, the agency said that other studies of PD-1 or PD-L1 inhibitors, in combination with immunomodulatory and anticancer drugs for myeloma, would be examined and possibly placed on hold.

According to a Roche press release, the FDA is currently evaluating all ongoing blood cancer trials investigating anti-PD-1/PD-L1 drugs in combination with immunomodulatory medications to determine if anti-PD-1/PD-L1 is a class-wide concern in myeloma and blood cancers, or a specific concern with certain combinations with immunomodulatory medicines.

More recently, the FDA suspended additional myeloma and lymphoma trials testing other combinations of PD-1 or PD-L1 drugs with immunomodulatory agents.

Bristol-Myers Squibb was the first to be notified that three of its checkpoint trials testing Opdivo would be put on hold.

Celgene, which had been testing Imfinzi (durvalumab) in similar combinations, was next. One Celgene study was suspended and five were placed on partial hold.