The jury remains out on the prospects of anti-TIGIT checkpoint inhibitors but Gilead and Arcus Biosciences are hoping to ease concerns that the modality is a bust, teasing new phase 2 data.
The two companies say that a duo of combination therapies including Arcus’ anti-TIGIT monoclonal antibody domvanalimab continue to show improvement against Arcus’ PD-L1 inhibitor alone, according to a release Monday.
Arcus and Gilead are testing a double combination of domvanalimab plus the anti-PD-L1 med zimberelimab in addition to a triplet combination of the TIGIT, PD-L1 and etrumadenant, an adenosine receptor antagonist. The open-label phase 2 trial, dubbed ARC-7, is assessing the combinations in patients with non-small cell lung cancer.
The latest interim analysis indicates that each of the combinations have shown clinically meaningful improvement compared to zimberelimab as a monotherapy in a number of measures including objective response rates and progression-free survival. The devil is in the details, however, and those remain under wraps. The companies say that more thorough data will be presented at an ASCO plenary session on December 20.
The prospective data offers a glimmer of hope for the potential subclass of checkpoint inhibitors that a number of drugmakers have bought into. A Fierce Biotech analysis found that as of May, Big Pharmas had bet north of $6 billion in deals for anti-TIGITs. But back-to-back phase 3 flops of Roche’s tiragolumab rattled confidence, with fellow player and GSK partner iTeos announcing shortly thereafter that it would be reevaluating its plans. GSK’s deal with iTeos topped the list of TIGIT deals, with more than $2 billion in biobucks on the line.
But at this year’s European Society for Medical Oncology annual meeting, oncologists and executives were quick to throw cold water on the idea that TIGITs were already a bust. Hesham Abdullah, head of global oncology development for GSK, told Fierce Biotech at the time that “it’s not always about being first” as TIGIT data began to roll in, although he noted that the Roche news was disappointing.
GSK is similarly testing its TIGIT candidate, GSK4428859, as part of a triplet therapy in combination with anti-PD-1 drug Jemperli and an investigational anti-CD96 med. In a later press conference at ESMO, Merck & Co.’s lead investigator for the company’s TIGIT trial similarly said it was too early to rule on the potential of the modality.
Melissa Johnson, M.D., director of lung cancer research at the Sarah Cannon Research Institute at Tennessee Oncology and lead investigator of ARC-7, said in the release that the data “reinforce confidence” in the pathway.
“The interim results show that combining two checkpoint inhibitors—an anti-TIGIT and an anti-PD-1—delivered added benefit beyond anti-PD-1 monotherapy in this setting,” she said. The two companies added that there were no unexpected safety signals identified as of the data cutoff.