TIGITs get another boost as Gilead-Arcus' domvanalimab scores high response in early gastric cancer data set
In another sign that anti-TIGIT antibodies may yet live up to some of the hype, Gilead Sciences has unveiled preliminary data showing that its Arcus Biosciences-partnered candidate domvanalimab is effective against gastric cancers in combo with Arcus’ anti-PD-1 drug.
The early readout comes from the first arm of the EDGE-Gastric study, which is investigating various combinations of domvanalimab with the anti-PD-1 antibody zimberelimab as well as chemotherapy in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma.
As of Sept. 4, there was an overall response rate of 80% among the 15 patients enrolled so far with PD-L1-high tumors who received a domvanalimab-containing regimen, Gilead reported. This dropped to 46% among the 24 patients with PD-L1-low tumors. There were two confirmed complete responses in the trial at that point.
The progression-free survival (PFS) rate was 93% among patients in the PD-L1-high group and 68% among the low cohort, Gilead added. Median PFS was not reached, and the Big Pharma is expecting to report mature data on that metric in the second half of next year.
Domvanalimab is the only FC-silent anti-TIGIT antibody in phase 3 trials for upper gastrointestinal adenocarcinomas, pointed out Gilead, which harbors hopes of the drug being the first TIGIT to market for these cancers.
FC receptors are found on the cell surface and contribute to the protective functions of the immune system by binding to antibodies that are attached to infected cells or invading pathogens. TIGITs are broadly split into those that have an FC receptor function—such as Roche’s tiragolumab —and those that have mutated out the receptor function, like domvanalimab.
“These data add to the growing body of evidence that domvanalimab, an FC-silent anti-TIGIT antibody, has a differentiated safety and tolerability profile relative to published data from studies with FC-enabled anti-TIGIT antibodies,” Gilead said in the postmarket release yesterday.
“These early data are encouraging and indicate the potential for the anti-TIGIT, domvanalimab-based therapy to improve upon anti-PD-1 and chemotherapy in this setting, with a similar safety profile to anti-PD-1 and chemotherapy,” said Memorial Sloan Kettering Cancer Center’s Yelena Janjigian, M.D., a principal investigator for study, in the release.
The preliminary data support an ongoing phase 3 study of the combo in unresectable or metastatic upper gastrointestinal cancers, the Big Pharma said. Various domvanalimab-containing regimens are also undergoing three separate lung cancer studies where they are going head-to-head with the likes of Merck & Co’s blockbuster Keytruda.
While still early days, Gilead and Arcus’ readout marks another promising clinical development for a once-hyped class of potential medicines that was knocked off track by a pair of phase 3 failures for Roche’s TIGIT tiragolumab in lung cancer last year.
Since then, tiragolumab has shown some promise in liver cancer, while Gilead and Arcus’ domvanalimab-zimberelimab combo was found to induce a 33% reduction in the risk of disease progression compared to zimberelimab alone.
Still, other Big Pharmas have withdrawn from the space. Bristol Myers Squibb recently terminated an anti-TIGIT from its phase 2 pipeline, while Novartis handed back ociperlimab to BeiGene in the summer.