Imfinzi Trial Does Not Meet Primary Endpoint

The KESTREL Phase III trial for AstraZeneca’s Imfinzi (durvalumab) did not meet the primary endpoint of improving overall survival (OS) versus the EXTREME treatment regimen (chemotherapy plus cetuximab), a standard of care, in the 1st-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors expressed high levels of PD-L1. Also, the combination of Imfinzi plus tremelimumab did not indicate an OS benefit in ‘all-comer’ patients, a secondary endpoint.

“Metastatic head and neck cancer is a complex and challenging disease with a poor prognosis. While we are disappointed by these results, insights from the KESTREL Phase III trial will advance our understanding and application of immunotherapy across our clinical development program. We will continue to build on the established benefits of Imfinzi in early lung cancer and small cell lung cancer, to bring immunotherapy treatment options to all patients who may benefit,” Dave Fredrickson, Executive Vice President, Oncology Business Unit, said.

The safety and tolerability profiles for Imfinzi as a monotherapy and in combination with tremelimumab were consistent with previous trials. The data will be shared in due course.

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.

The KESTREL Phase III trial was a randomized, open-label, multi-center, global trial in the 1st-line treatment of recurrent or metastatic HNSCC. 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.

The trial was conducted in more than 200 centers across 23 countries, including centers in the US, Europe, South America and Asia. The primary endpoint was OS in patients with high PD-L1 expression in the Imfinzi monotherapy arm. OS in ‘all-comer’ patients treated with the combination of Imfinzi plus tremelimumab was being tested as a key 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, based on the PACIFIC Phase III trial. Additionally, it is approved in the EU, US, Japan and many other countries for the treatment of extensive-stage small cell lung cancer (SCLC) based on the CASPIAN Phase III trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and several other countries.

As part of a broad development program, Imfinzi is being tested as a monotherapy and in combination with other anti-cancer treatments for patients with NSCLC, SCLC, bladder cancer, hepatocellular carcinoma (HCC), biliary tract cancer, oesophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer and other solid tumors.

Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation, priming the immune response to cancer and fostering cancer cell death. Tremelimumab is being tested in a clinical trial program in combination with Imfinzi in NSCLC, SCLC, bladder cancer and HCC.