ASCO: Gilead, Arcus inject a bit more hope into TIGIT tale with reduced risk of lung cancer progression

Gilead Sciences and Arcus have added another glimmer of hope that the anti-TIGIT class has a place among checkpoint inhibitors to treat lung cancer, thanks to updated phase 2 data showing a reduction in the risk of disease progression. 

The two companies took to the American Society of Clinical Oncology (ASCO) annual meeting Saturday to provide an update on a phase 2 trial testing anti-TIGIT monoclonal antibody domvanalimab in first-line patients with metastatic non-small cell lung cancer. With data now available on all 150 evaluable patients, domvanalimab in combination with anti-PD-1 zimberelimab was found to have a 33% reduction in the risk of disease progression compared to zimberelimab alone. When the two meds were tacked onto a third checkpoint inhibitor from Arcus, A2a/b adenosine receptor antagonist etrumadenant, the risk reduction fell slightly to 28% compared to zimberelimab alone. 

When the companies reported data at the ASCO plenary sessions in December, no complete responses had been found. Now, two have been recorded, one in the zimberelimab monotherapy cohort and another in the combo arm with domvanalimab. The objective response rate of the doublet combo was 40%, while the triplet was 44%. The ORR for zimberelimab alone was 30%. 

“[The results] shows the consistency of the TIGIT arms showing enhanced response rates and enhanced PFS and supports our ongoing pivotal registration trials,” said Gilead’s oncology chief Bill Grossman, M.D., Ph.D., in an interview with Fierce Biotech. 

TIGITs have become a class of checkpoint inhibitors shrouded in unease as an early batch of poor showings from Roche in lung cancer forced pharmas to defend their early investments in the class. Companies like Merck & Co., GSK, Novartis and Gilead Sciences all have their hands in the TIGIT cookie jar and have insisted that their bets will pay off. And newer data suggest that the mechanism can in fact add value when tacked onto PD-L1s. 

Roche reported in late May that a triple combo therapy of its anti-TIGIT tiragolumab with Tecentriq and Avastin had a 42.5% objective response rate in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma. That’s sizably better than the 11.5% response rate for standard of care, which was Tecentriq or Avastin alone. Now, Gilead is adding to the good news pile. 

“We definitely continue to have conviction in this space,” said Grossman, adding that Gilead did not “go wild” in the registrational trials, limiting use to patients with lung or upper GI cancers, which was validated by “the most compelling” clinical data in-house. He conceded that “it’s been an interesting ride.” 

Grossman also stood by the safety profile of the combination therapies, with side effects reported in 98% of patients in both the doublet and triplet arms. Almost 1 in 5 patients in each of the combo cohorts dropped out due to side effects. But he was encouraged by the low amount of infusion-related reactions, affecting just 4% of the doublet arm and 12% of the triplet arm. 

“The safety profile has been really consistent and very manageable,” he said, attributing that in part to the Fc-silencing component of domvanalimab. The Fc region on antibodies has the tendency to spur cytotoxicities when interacting with Fc receptors on cells. 

While most of the attention on this trial will be directed toward the anti-TIGIT, the value and impact of etrumadenant is also up for inspection. Grossman said that Gilead is “continuing to evaluate the adenosine assets,” which includes CD73 inhibitor quemliclustat. Arcus received $725 million when Gilead elected to take on the two TIGIT programs, etrumadenant and quemliclustat.

Editor's note: This story was updated to correct the objective response rates in ARC-7 trials.