AZ’s Immune Checkpoint Inhibitor Flunks Head and Neck Cancer Trial

On February 5th, AstraZeneca announced that the KESTREL Phase 3 trial, which evaluated its PD-L1 antibody, failed to deliver desired results. Imfinzi (durvalumab) did not meet the primary endpoint of improving overall survival (OS) as a first-line treatment in recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) patients as compared to the standard of care.

Besides, the trial also missed the secondary endpoint of delivering OS benefit in patients who received the Imfinzi plus tremelimumab combo therapy. The Phase 3 trial was conducted in more than 200 centers across 23 countries, including centers in the US, Europe, South America, and Asia.

Nearly 750,000 patients were diagnosed with Head and Neck cancer globally in 2020 with 65,000 cases in the US alone. Besides, treatment costs are also pretty high for this condition.

“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 3 trial will advance our understanding and application of immunotherapy across our clinical development programme,” said Dave Fredrickson, Executive VP, Oncology Business Unit, AstraZeneca.

Imfinzi & Tremelimumab Checkpoint Inhibitors

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

The drug is previously approved for stage 3 NSCLC after chemoradiation therapy in the EU, US, Japan, China, and many other countries. The drug is currently being tested as a monotherapy and in combination with other treatments for patients with NSCLC, SCLC, bladder cancer, hepatocellular carcinoma, and nine other cancers.

Tremelimumab is a human monoclonal antibody and potential new medicine that blocks the activity of CTLA-4, contributing to T cell activation, priming the immune response against cancer, and fostering cancer cell death. AstraZeneca is pursuing a comprehensive clinical trial program for Imfinzi in combination with tremelimumab in multiple tumor types.

AstraZeneca: Pipeline and Past Work

Imfinzi has been a successful drug for AstraZeneca with 43% growth in 2020 raking in more than $400 million. While it is unfortunate that the drug faltered in the Phase 3 trial, AstraZeneca still has promising immune-oncological treatments in its pipeline.

Monalizumab is a first-in-class humanized anti-NKG2A (natural killer cell receptor) antibody, which is being tested in combination with cetuximab (chimeric monoclonal antibody used for colorectal cancer) in the INTERLINK-1 Phase 3 trial in patients with recurrent or metastatic HNSCC previously treated with IO and chemotherapy.

AstraZeneca obtained full oncology rights to monalizumab from Innate Pharma in October 2018 through a co-development and commercialization agreement initiated in 2015. The company boasts of seven new medicines in its’ oncology pipeline that was launched between 2014 and 2020.

Related Article: With their Respective Immunotherapy Drugs, Arcus, AstraZeneca Combine to Combat Lung Cancer

References

1. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/update-on-kestrel-phase-iii-trial-for-imfinzi.html#!

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Author

Eduardo Longoria