Gilead Sciences and Arcus Biosciences have decided to ‘deprioritise’ the further development of their A2 receptor antagonist, etrumadenant, in metastatic castrate-resistant prostate cancer (mCRPC) after reviewing radiographic progression-free survival data from a phase 1b/2 study of the drug.
The ARC-6 trial has been evaluating etrumadenant in combination with zimberelimab and docetaxel versus docetaxel in mCRPC patients.
While the trial will continue to completion, Arcus said in a statement: “Based on our most recent analysis of data from ARC-6, the etrumadenant-based combination is not expected to demonstrate sufficient clinical benefit in castrate resistant prostate cancer to warrant further investment.”
mCRPC is a form of prostate cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone. Up to 20% of patients with prostate cancer develop mCRPC within five to seven years of diagnosis.
Etrumadenant is a small molecule, selective dual antagonist of the A2a and A2b receptors, which are expressed on the surface of immune cells and mediate the immunosuppressive effects of adenosine, produced inside tumours as a result of rapid cancer cell turnover.
Once the immunosuppressive effects of adenosine are blocked, activation of antitumour immune cells may be restored, which could result in tumour cell death.
The candidate is also being assessed alongside zimberelimab and chemotherapy in second- and third-line metastatic colorectal cancer. The phase 1b/2 ARC-9 trial is fully enrolled, with data expected in the first half of next year.
The two companies entered into a ten-year collaboration in May 2020, under which Gilead obtained time-limited exclusive option rights to all of Arcus’ clinical programmes arising during the collaboration term.
Besides etrumadenant, the partners are co-developing four investigational products, including anti-PD-1 molecule zimberelimab, anti-TIGIT antibody domvanalimab and CD73 inhibitor quemliclustat.
Terry Rosen, chief executive officer of Arcus, said: “By early next year, we expect to present several key datasets across our pipeline, including data from our phase 2 EDGE-Gastric study for domvanalimab in first-line gastric cancer, overall survival data from ARC-8 for quemliclustat in pancreatic cancer, and data from the phase 1b ARC-20 study for AB521, our HIF-2a inhibitor.”