Arcus, Gilead drop A2R inhibitor in prostate cancer after glimpsing early data

Arcus Biosciences and Gilead have decided not to advance their A2R inhibitor in prostate cancer after taking a look at some early clinical data.

The two companies are studying the candidate, called etrumadenant, in trials of various cancers in combination with chemo and other drugs. One of these trials, a phase 1b/2 study dubbed ARC-6, had been exploring a combination of etrumadenant plus Arcus’ China-approved lymphoma drug zimberelimab and the chemotherapy docetaxel to treat metastatic castrate-resistant prostate cancer (mCRPC).

Having reviewed radiographic progression-free survival data from the trial, Arcus said the combo treatment “is not expected to demonstrate sufficient clinical benefit in castration-resistant prostate cancer to warrant further investment.”

While the study will be allowed to complete, the companies have decided to deprioritize any further development of etrumadenant in mCRPC, Arcus said in its second-quarter earnings report.

Another phase 1b/2 trial, called ARC-9, that is evaluating a etrumadenant-zimberelimab-chemo combo in mCRC is already fully enrolled and is expected to read out in the first half of 2024, Arcus added.

Prostate cancer was only one arrow in etrumadenant’s quiver. The A2a/A2b adenosine receptor antagonist is also being assessed as part of combination treatments across two lung cancer trials as well as for colorectal cancer.

Etrumadenant appeared to show its worth at the American Society of Clinical Oncology (ASCO) annual meeting in June. It was at that conference that Gilead and Arcus provided an update on a phase 2 trial testing anti-TIGIT monoclonal antibody domvanalimab in combination with zimberelimab that demonstrated a 33% reduction in the risk of lung cancer progression compared to zimberelimab alone. When etrumadenant was added to the mix, the risk reduction fell slightly to 28% compared to zimberelimab alone.

Gilead first partnered with Arcus on etrumadenant in a $725 million deal back in 2021 that also spanned the anti-TIGIT drugs domvanalimab and AB308 as well as the CD73 inhibitor quemliclustat.