AstraZeneca delivers rare win for treme in liver cancer, bouncing back from flops to beat Bayer's Nexavar

Susan Galbraith
Susan Galbraith, executive vice president of oncology R&D at AstraZeneca (AstraZeneca)

Can AstraZeneca pick its CTLA-4 inhibitor up off the canvas? After seeing the drug knocked down by a series of setbacks, AstraZeneca has now reported improved survival in a phase 3 checkpoint inhibitor combination study in liver cancer patients.  

The idea of combining antibodies against CTLA-4 and PD-1/L1 is well established from Bristol Myers Squibb’s work to pair Opdivo and Yervoy. Yet, AstraZeneca’s multiyear, multistudy effort to carve out a niche for its equivalent combination has been beset by failures. AstraZeneca has shown the PD-L1 part of the cocktail, Imfinzi, works, but at times the CTLA-4 drug tremelimumab has appeared to do more harm than good.

Now, AstraZeneca has added to the very short list of wins for tremelimumab. The study enrolled 1,324 patients with unresectable, advanced liver cancer to receive Bayer’s Nexavar or a novel dose and schedule of tremelimumab and Imfinzi as a first-line treatment. Patients in the experimental cohort received one priming dose of tremelimumab added to Imfinzi, followed by doses of the PD-L1 drug every four weeks. 

The clinical trial linked the tremelimumab-Imfinzi regimen to a statistically significant improvement in overall survival compared to Nexavar. Tremelimumab appears to be contributing to the benefits. The administration of Imfinzi as a monotherapy failed to improve statistically on the overall survival seen in the Nexavar cohort, although it did beat the Bayer drug numerically. 

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“This is the first time a dual immunotherapy regimen has improved overall survival as a first-line treatment for patients with unresectable liver cancer for whom treatment options are limited and long-term outcomes are poor,” Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, said in a statement.

AstraZeneca is yet to share data from the study, but the top-line findings are positive. As well as the primary endpoint success, AstraZeneca saw a “favorable” safety profile and found no evidence that the use of tremelimumab increases severe liver toxicity. 

The study points to a potential path to market for tremelimumab. Previously, tremelimumab’s only success came in the POSEIDON non-small cell lung cancer clinical trial. The liver cancer win could still be tarnished as more data emerge, but, for now, AstraZeneca can bask in a rare primary endpoint hit.