AstraZeneca’s tremelimumab fails another phase 3 cancer trial

AstraZeneca’s tremelimumab has come up short in another phase 3 trial. Having failed to improve outcomes in metastatic non-small cell lung cancer (NSCLC), the anti-CTLA4 antibody has now missed the primary endpoint in a phase 3 advanced head and neck cancer trial.

After ceding a head start to Bristol-Myers Squibb and Merck in the PD-1/PD-L1 space, AstraZeneca looked to a dual checkpoint blockade approach featuring tremelimumab to help it carve out a piece of the immuno-oncology market. The strategy was underpinned by a belief that blocking CTLA4 and PD-1/PD-L1 would yield better outcomes than monotherapies against either target in isolation.

The dual blockade approach has brought some success for Bristol-Myers, which has picked up FDA nods for its Opdivo-Yervoy combination in melanoma, renal cell carcinoma and metastatic colorectal cancer. AstraZeneca’s dual blockade program has hit some bumps in the road, though.

The latest setback comes from a phase 3 trial in patients with recurrent or metastatic head and neck squamous cell carcinoma who had progressed following platinum-based chemotherapy. Participants in the trial received either Imfinzi, the anti-PD-L1 antibody in combination with tremelimumab or standard of care chemotherapy.

Neither the Imfinzi monotherapy nor the tremelimumab combination resulted in a longer overall survival than was achieved by standard of care chemotherapy, resulting in the clinical trial missing its primary endpoint. The failure dents AstraZeneca’s hopes of bringing tremelimumab to market in head and neck cancer, but there remains a chance other data will revitalize the strategy.

“We look forward to seeing the results of the phase 3 Kestrel trial of Imfinzi and tremelimumab in patients who have not received prior chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma in the first half of 2019,” AstraZeneca Chief Medical Officer Sean Bohen said in a statement.

Kestrel is one of a clutch of ongoing clinical trials that will dictate whether tremelimumab has a future. AstraZeneca is assessing the anti-CTLA4 antibody together with Imfinzi as a first-line therapy in NSCLC in two phase 3 trials and is running late-phase studies of the combination in other diseases including hepatocellular carcinoma, urothelial cancer and small-cell lung cancer.

The breadth of the late-phase program means AstraZeneca still has plenty of chances to deliver the data it needs to get tremelimumab to market. But the phase 3 data generated so far give little cause for optimism. If anything, tremelimumab looked to hinder, not help, Imfinzi in the Mystic NSCLC trial, and has now added advanced head and neck cancer trial to its list of late-phase failures.