AstraZeneca’s Phase 3 KESTREL Trial of Imfinzi Fails to Meet the Primary Endpoint in Patients with Head and Neck Cancer

AstraZeneca’s Phase 3 KESTREL Trial of Imfinzi Fails to Meet the Primary Endpoint in Patients with Head and Neck Cancer TrialsiteN

AstraZeneca reported that its Phase 3 KESTREL trial of Imfinzi (durvalumab) failed to meet the primary endpoint of improving overall survival (OS) compared to the EXTREME treatment regimen (chemotherapy plus cetuximab, a standard of care). The trial was designed to evaluate the two therapies in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors expressed high levels of PD-L1. 

The randomized, open-label, global KESTREL trial was conducted in more than 200 centers across 23 countries, including the US, Europe, South America and Asia. The trial tested Imfinzi or Imfinzi plus a second immunotherapy, tremelimumab, versus the EXTREME treatment regimen (cetuximab with cisplatin or carboplatin plus 5-fluorouracil), a standard of care treatment. High PD-L1 was defined as either 50% or more tumor cells or 25% or more tumor-infiltrating immune cells expressing PD-L1. In addition to not reaching the primary endpoint, the combination of Imfinzi plus tremelimumab did not indicate an OS benefit in ‘all-comer’ patients, a secondary endpoint.

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) after chemoradiation therapy in the EU, US, Japan, China and many other countries. Additionally, it is approved in the EU, US, Japan and many other countries for the treatment of extensive-stage small cell lung cancer (SCLC). Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and several other countries.

About head and neck squamous cell carcinoma
Nearly 750,000 patients were diagnosed with head and neck cancer around the world in 2020. Two thirds of these patients are diagnosed in advanced stages, and more than half of those treated eventually relapse. Median survival for a patient with an uncurable or metastatic relapse remains under one year. More than 90% of all head and neck cancers start in the squamous cells that line the mouth, nose and throat and are called head and neck squamous cell carcinomas.