Gilead Sciences and Arcus Biosciences’ anti-TIGIT antibody domvanalimab has been tied to median overall survival of close to 27 months, keeping alive one of the last remaining hopes for this once-hyped modality.
The phase 2b study is evaluating various combinations of domvanalimab and Gilead and Arcus’ investigational anti-PD-1 antibody zimberelimab in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma.
Sunday, the companies unveiled the first overall survival data for the 41 patients in arm A1 of the study, who received 1600 mg of domvanalimab and 480 mg of zimberelimab intravenously every four weeks along with chemotherapy. This cohort demonstrated a median OS of 26.7 months.
In the Oct. 12 release, Arcus including a statement from Sun Young Rha, Ph.D., director of the Songdang Institute for Cancer Research in Korea, who described these OS data as “well beyond what would be required to demonstrate clinically meaningful benefit over standard of care.”
The latest slice of data also showed a confirmed overall response rate of 59% as well as median progression-free survival of 12.9 months, which Arcus said was consistent with prior reporting from the study.
Yesterday’s “promising results” reinforce Arcus’ confidence in the ongoing phase 3 study of domvanalimab and zimberelimab in 1,050 participants with the same range of cancers as the phase 2 trial, according to the biotech’s chief medical officer Richard Markus, M.D., Ph.D.
Domvanalimab is one of the last TIGIT candidates still standing, after high-profile clinical failures saw the likes of Roche, GSK and BeOne Medicines retreat from a modality that was once hailed as the future of immuno-oncology.
Most of those discarded candidates were Fc-enabled, meaning the antibodies retain a fully functional Fc region to bind to Fc receptors found on the cell surface and contribute to the protective antitumor functions of the immune system. In contrast, domvanalimab is known as Fc-silent, meaning the Fc function has been mutated out.
The only other TIGIT candidate still in the running—AstraZeneca’s TIGIT/PD-1 bispecific antibody rilvegostomig—uses an Fc-silent anti-TIGIT antibody from Compugen.
“These survival results add to the totality of data for domvanalimab and the role of anti-TIGIT-based combinations for the treatment of different cancers and reinforce our conviction that an Fc-silent anti-TIGIT antibody may provide differentiated efficacy and safety,” Arcus’ Markus said in yesterday’s release.