AstraZeneca's novel checkpoint inhibitor flunks first phase 3, denting partner's share price

AstraZeneca's first phase 3 bet on the anti-NKG2A antibody monalizumab has ended in failure. Adding the Innate Pharma-partnered molecule to Eli Lilly's Erbitux failed to improve outcomes in head and neck cancer patients at an interim analysis, prompting AstraZeneca to stop the study.

Innate and AstraZeneca moved monalizumab into phase 3 development in patients with recurrent or metastatic squamous cell carcinoma of the head and neck in 2020 on the strength of evidence that blockading the checkpoint pathway boosts activation of natural killer cells. In a phase 2 expansion cohort, giving the investigational drug to 40 prior recipients of platinum-based therapy and a PD-L1 inhibitor resulted in an overall response rate of 20%.

AstraZeneca is yet to share data from the phase 3 study, which set out to enroll around 600 patients in 2020, but whatever the independent data monitoring committee learned failed to make the case for the continuation of the clinical trial. On the recommendation of the committee, AstraZeneca is stopping the study early.  

The failure removes one shot on goal for monalizumab. With investigators seeing no new safety findings in the head and neck cancer study, AstraZeneca and Innate are pushing ahead with a phase 3 clinical trial in the unresectable stage 3 non-small cell lung cancer setting as well as with a phase 2 neoadjuvant lung cancer study. 

Innate CEO Mondher Mahjoubi talked up the prospect of monalizumab working in lung cancer despite failing in head and neck cancer. Mahjoubi’s confidence is underpinned by data from randomized phase 2 clinical trials in the two lung cancer settings. Innate has a long wait to show whether Mahjoubi’s confidence is justified, with the recently initiated phase 3 PACIFIC-9 study set to reach its primary completion in 2026.

Shares in Innate, which has a cash runway that continues into 2024, fell 20% in early trading in Paris on news of the phase 3 failure, dragging the biotech’s stock price down to below 2.50 euros ($2.55). The stock is down more than 40% so far this year.