FDA Places Partial Clinical Hold on Enrolment of Durvalumab Trials in HNSCC

The U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on the enrolment of new patients with head and neck squamous cell carcinoma (HSNCC) to clinical trials evaluating durvalumab as a single agent and in combination with tremelimumab or other potential agents, according to an announcement by AstraZeneca.¹

The FDA’s decision comes after voluntary action by AstraZeneca to pause enrolment of new patients with HNSCC until a detailed analysis of bleeding-related adverse events is conducted. Researchers observed these adverse reactions during routine safety monitoring of the phase 3 KESTREL (ClinicalTrials.gov Identifier: NCT02551159) and EAGLE (ClinicalTrials.gov Identifier: NCT02369874) trials.

AstraZeneca has submitted its analysis of the observed bleeding events to the FDA for review and is working closely with the agency to resume patient enrolment as quickly as possible.

The partial clinical hold on new patient enrolment relates only to clinical trials for patients with head and neck cancer. Studies evaluating durvalumab monotherapy and combination therapy in other cancer types are continuing as planned. Pivotal data from a trial in lung cancer is expected in the first half of 2017.

Previous reports of studies assessing durvalumab in patients with metastatic or recurrent HSNCC show an objective response rate of 11% overall and 18% in those with high PD-L1 expression. Six-month and 12-month overall survival is 62% (95% CI, 48-74) and 42% (95% CI, 27-55), respectively.

In 2015, durvalumab received Fast Track Designation for the treatment of patients with PD-L1-positive metastatic HNSCC, and in 2016, durvalumab was granted Breakthrough Therapy Designation by the FDA for the treatment of patients with PD-L1-positive inoperable or metastatic urothelial bladder cancer whose tumor has progressed during or after 1 standard platinum-based regimen.                      

Reference

1. AstraZeneca head and neck cancer trials. AstraZeneca website. https://www.astrazeneca.com/media-centre/press-releases/2016/astrazeneca-head-and-neck-cancer-trials-27102016.html. Updated October 27, 2016. Accessed October 31, 2016.