Arcus says early data for anti-TIGIT domvanalimab combos look good, but mum on details

Arcus Biosciences on Wednesday said a Phase II study testing combinations of its anti-TIGIT monoclonal antibody domvanalimab (AB154), which is partnered with Gilead Sciences, showed "encouraging" results when given as first-line treatment to PD-L1-high patients with metastatic non-small-cell lung cancer (NSCLC). The ARC-7 trial is also evaluating Arcus' PD-1 inhibitor zimberelimab (AB122) as monotherapy, with the company reporting that the drug "showed activity similar to that of marketed anti-PD-1 antibodies studied…in this setting."

Shares in Arcus, which did not reveal any specific data from the trial, zigzagged in after-hours trading, tumbling as much as 9% shortly after making its announcement, before jumping to 18% higher than where it closed.

ORR positive, PFS not yet assessed

The three-arm ARC-7 study includes 150 patients with PD-L1 ≥ 50% and EGFR/ALK wild-type, metastatic NSCLC. Participants were randomised to first-line treatment with zimberelimab alone, or in combinations with domvanalimab, or with domvanalimab plus Arcus' dual adenosine A2a/A2b receptor antagonist etrumadenant (AB928). The company said that at the first interim analysis, both arms with domvanalimab-based combinations showed "encouraging clinical activity" on the co-primary endpoint of objective response rate (ORR). It noted that the data were not yet mature, and the second co-primary endpoint of progression-free survival (PFS) was not assessed.

At the time of data cut-off, there were no unexpected safety signals, and the current safety profile for each arm of the study appears to be "consistent with known immune checkpoint inhibitors in this setting," according to the company. The ARC-7 data will be submitted later this year for presentation at a medical conference. Meanwhile, it said the ongoing Phase III ARC-10 trial will continue to enroll as planned. That three-arm study is evaluating first-line zimberelimab, alone and together with domvanalimab, against platinum-based chemotherapy in about 625 locally advanced or metastatic NSCLC patients with PD-L1>50%.

Gilead opt-in decision looms

Gilead entered into a long-term immunotherapy partnership with Arcus last year, giving it immediate rights to zimberelimab, as well as opt-in rights to domvanalimab and etrumadenant. According to Arcus, Gilead is expected to decide later this year whether to take up the anti-TIGIT programme. If it does, Arcus stands to pocket up to $500 million in potential future US regulatory approval milestones.

Bill Grossman, chief medical officer at Arcus, said "next steps are to complete enrollment in all our open domvanalimab studies, execute on our broader plans for Phase III studies for domvanalimab across multiple cancer types, and further explore combinations with domvanalimab and etrumadenant."

Domvanalimab is an Fc-silent monoclonal antibody that binds to the TIGIT protein receptor on immune cells. Arcus is also developing a second anti-TIGIT candidate, dubbed AB308, which is an Fc-enabled monoclonal antibody currently in Phase I development, with a potential focus on haematological malignancies.