FDA Places Holds on Imfinzi Trials Following Unexplained Deaths in Keytruda Trials

FDA Places Holds on Imfinzi Trials Following Unexplained Deaths in Keytruda Trials

The U.S. Food and Drug Administration (FDA) has placed a partial hold on two clinical trials testing a combination of AstraZeneca‘s Imfinzi (durvalumab) with an immunomodulatory drug in lymphoma and leukemia patients.

The agency also placed a partial hold on three other myeloma trials testing similar Imfinzi combinations, halting further enrollment but allowing patients who have shown clinical benefits to remain on treatment.

One additional myeloma trial was suspended, and all participants must stop taking the investigational drug. Also, no new participants may be recruited to the study.

The decision was not based on safety concerns in these clinical trials, but rather on excessive deaths seen in other trials testing Keytruda (pembrolizumab) — a drug with a similar mechanism of action — in combination with the immunomodulatory agent Revlimid (lenalidomide) and low-dose dexamethasone.

Imfinzi is a human monoclonal antibody directed against the PD-L1 protein, blocking its interaction with the PD-1 receptor. Keytruda blocks PD-1 directly. Both drugs are used to counteract the tumor’s immune-evading tactics and induce an immune response.

Celgene is currently investigating Imfinzi in two lymphoma trials: the Phase 1/2 MEDI4736-NHL-001 (NCT02733042) and the Phase 2 MEDI4736-DLBCL-001 (NCT03003520). Both were placed on partial hold.

The Phase 1/2 study is testing Imfinzi as a monotherapy or combined with other therapies. In one treatment arm of the study, patients were receiving Imfinzi plus Revlimid with or without Rituxan (rituximab). Other treatment arms included the combination of Imfinzi plus Imbruvica (ibrutinib), or Imfinzi plus Levact (bendamustine) with or without Rituxan. Only the Revlimid arm was affected by the clinical hold, and the trial will continue to enroll in the other arms as planned.

The Phase 2 study is evaluating Imfinzi plus Rituxan and chemotherapy, with or without Revlimid, in subjects with previously untreated high-risk diffuse large B-cell lymphoma.

In July, due to a significant number of deaths, the FDA suspended two of Merck’s Keytruda clinical trials, and placed another on hold. The decision was later extended to three Bristol-Meyers Squibb trials investigating Opdivo (nivolumab), which also targets the PD-1/PD-L1 pathway.

Celgene researchers said that no safety concerns had been detected in the company’s trials with Imfinzi, but the clinical hold will allow them to gather additional information.

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