Tanja Obradovic Highlights Rilvegostomig’s Unique MoA in AstraZeneca’s TIGIT Program
Tanja Obradovic, Oncology Medical Strategy Advisor at Mercurial AI, shared on LinkedIn:
“Development strategies and decision making dynamics around targeting T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domain (TIGIT) by different Pharma and Biotech offers valuable learnings.
Roche’s anti-TIGIT MAb tiragolumab failed last of the Skyscraper trials (1st line for liver cancer Phase III) so that program is now over. Tiragolumab program was extensive with 12 late stage trials set rapidly in motion based on preclinical and limited early clinical data that raises questions if more measured and staggered approach around early interim analysis on trials and other NoGo / Go decisions would avoid lengthy perseverance and involvement of thousands of patients that did not derive benefit. Especially considering already negative data for TIGIT inhibitors developed by competitors such as Merck and iTeos Therapeutics (in partnership with GSK) on numerous trials that resulted in program eliminations earlier.
Despite mounting evidence against the TIGIT mechanism two companies are still in the game. Arcus Biosciences is not widening program and has two ongoing trials awaiting critical read-outs for TIGIT inhibitor domvanalimab. Arcus recently announced that abstract describing OS data from the Phase II EDGE-Gastric study, evaluating domvanalimab plus zimberelimab and chemotherapy in upper GI adenocarcinomas, will be presented at the 2025 ESMO Congress in October.
Unlike others, AstraZeneca is going into other direction and has very large program for anti-TIGIT x PD-1 bispecific rilvegostomig with 24 recruiting trials including 10 of the Phase II and 10 Phase III trials. Latest addition that opened mid July is GEMINI-PeriOp Phase II platform trial (NCT07069712, one arm containing rilvegostomig) in perioperative setting for resectable gastroesophageal adenocarcinoma.
In the case of rilvegostomig, hopes of good efficacy and safety profile despite poor record within the class are pinned upon mechanism of action that has some unique aspects. Rilvegostomig anchors itself to TIGIT before targeting PD-1 leading to enhanced immune activation and improving anti-tumor responses. Rilvegostomig also minimizes the unwanted depletion of TIGIT-expressing effector immune cells leading to likely cleaner safety profile than the one of potential combination of separate inhibitors for PD(L)-1 and TIGIT. As read-outs happen it will be of interest to observe how fast strategy reaction and regulatory feed back will be around troubled TIGIT targeting.
Considering massive size of the rilvegostomig program, historical record in similar situations and complexity of TIGIT biology it is a risky strategy closely watched for outcome.”
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