FDA Slaps Clinical Hold on AstraZeneca PLC's Phase III Head and Neck Cancer Program
October 27, 2016
By Alex Keown, BioSpace.com Breaking News Staff
LONDON -- Shares of AstraZeneca are down more than 4 percent following an announcement that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on new patient enrollment to the company’s Phase III clinical trial of durvalumab for head and neck squamous cell carcinoma.
AstraZeneca is investigating durvalumab as a monotherapy treatment for HNSCC, as well as in combination with tremelimumab and other drugs for other cancers. Patients already enrolled in the trial will continue to receive doses of durvalumab. Additionally, AstraZeneca said the partial hold only concerns the HNSCC trial and does not affect trials of durvalumab in other cancers, including lung cancer.
The FDA slapped the partial hold onto the trial following reports of adverse events related to bleeding. In its statement, AstraZeneca said the FDA’s decision to place the partial hold on the trial followed the company’s voluntary decision to do so while the company investigated. AstraZeneca said the bleeding reports part of routine safety monitoring of the Phase III KESTREL and EAGLE trials. Bleeding is a known complication in treatments of head and neck cancers primarily due to the nature of the underlying disease, the proximity of tumors to major blood vessels and use of prior cancer therapies, which may involve surgery and radiation, AstraZeneca said this morning. In its announcement, AstraZeneca said it has submitted its analysis of the bleeding events to the regulatory agency for review and is working to resolve the issues and open the trial back up to enrollment.
Durvalumab is a monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. By inhibiting PD-L1, durvalumab helps increase T-cell activity against the tumor to counter its efforts to evade the immune system, according to AstraZeneca. In 2015, durvalumab received Fast Track Designation for the treatment of patients with PD-L1-positive metastatic HNSCC.
The safety concerns are not new and date back at least a month, Endpoints reported. AstraZeneca told the trade publication that it took steps to halt enrollment of new patients in mid-September. A company spokesperson told Endpoints that AstraZeneca hopes to resume enrollment soon.
AstraZeneca has had some issues with durvalumab before. The company halted two clinical trials testing the combination of its experimental AZD9291 and durvalumab for lung cancer following reports of patients developing interstitial lung disease-like problems in one trial.
Delays from the partial hold on durvalumab could impact how the market responds to the drug, should it pass through regulatory hurdles. Endpoints said the company will be forces to “play catch up to the market leaders in checkpoint inhibitors.” AstraZeneca will slide back to the fourth or fifth position in the market, behind Roche ’s Tecentriq, Merck ’s Keytruda and of course, Bristol-Myers Squibb ’s Opdivo.