Drugs

FDA PD-1 Concerns Spread to AstraZeneca/Celgene Trials

David McFarland

— 2 min read
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FDA concerns about PD-1/PD-L1 inhibitors have spread to clinical trials conducted by AstraZeneca and Celgene, with clinical holds ordered on their new development program. Last week, CDER director Janet Woodcock said the agency was stepping up its safety surveillance on PD-1/PD-L1 inhibitors after an investigational clinical trial involving Merck’s Keytruda (pembrolizumab) in combination with other therapies in multiple myeloma patients “found an excess of deaths for patients receiving Keytruda when combined with these other drugs.” The agency, she said, is working with sponsors of similar cancer drugs to examine other trials in which these drugs are being studied in combination with other drugs.

 

As a result, AstraZeneca says development partner Celgene has been issued a partial clinical hold on five trials and a full clinical hold on one trial in the Celgene FUSION program. In 4/2015, Celgene entered into a strategic collaboration with AstraZeneca’s MedImmune biologics arm to develop Imfinzi (durvalumab) for hematologic malignancies. The affected trials are testing durvalumab, an anti-PD-L1 agent, in combination with immunomodulatory agents, with or without chemotherapy, in blood cancers such as multiple myeloma, chronic lymphocytic leukemia and lymphoma. “No imbalance has been observed in the FUSION program; however, the clinical holds allow for additional information to be collected to further understand the risk benefit profile of the program,” AstraZeneca says.

 

Patients enrolled in the trials on partial clinical hold who are receiving clinical benefit from treatment may remain on treatment, the company says. Patients enrolled in the trial on full clinical hold will be discontinued from treatment.

 

The trials placed on partial clinical hold are:

  • MEDI4736-MM-001: A Phase 1b multicenter, open-label study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with pomalidomide with or without low-dose dexamethasone in patients with relapsed and refractory multiple myeloma
  • MEDI4736-MM-003: A Phase 2, multicenter, open-label study to determine the safety and efficacy for the combination of durvalumab and daratumumab in patients with relapsed and refractory multiple myeloma
  • MEDI4736-MM-005: A Phase 2, multicenter, single-arm study to determine the efficacy for the combination of durvalumab plus daratumumab in patients with relapsed and refractory multiple myeloma that have progressed while on current treatment regimen containing daratumumab
  • MEDI4736-NHL-001: A Phase 1-2, open-label, multi-center study to assess the safety and tolerability of durvalumab as monotherapy and in combination therapy in subjects with lymphoma or chronic lymphocytic leukemia. 
  • MEDI4736-DLBCL-001: A Phase 2, open-label, multicenter study to evaluate the safety and clinical activity of durvalumab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) or with lenalidomide plus R-CHOP in patients with previously untreated, high risk diffuse large B Cell lymphoma

The trial on full clinical hold is:

  • MEDI4736-MM-002: A Phase 1b multicenter, open-label study to determine the recommended dose and regimen of durvalumab in combination with lenalidomide with and without low-dose dexamethasone in subjects with newly diagnosed multiple myeloma

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