Tanja Obradovic, Senior Advisor of Oncology Drug Development at HopeAI, Consultant, Oncology Drug Development at Arc Nouvel Clinical Development Consulting, and Oncology Medical Strategy Advisor at Mercurial AI, shared a post on LinkedIn:
“Just announced stopping of one more large Phase III testing TIGIT as a target with domvanalimab by Arcus Biosciences in upper gastrointestinal cancers
It is joining long list of many TIGIT program cancellations due to disappointing results across many studies (my article from few moths ago) on actions by Merck, Roche, BeOne Medicines, Agenus and iTeos Therapeutics.
After this outcome in gastric cancer domvanalimab is still tested in two other phase III trials, both in first-line lung cancer: Star-121 tests a zimberelimab plus chemo triplet versus keytruda plus chemo in first-line metastatic disease, while Pacific-8 gives domvanalimab on top of imfinzi in stage III NSCLC. Based on history of others and latest from STAR-221 probability of success of these trials is low.
This leaves only one still significant TIGIT targeting ongoing program -bispecific MAb, rilvegostomig by AstraZeneca. Rilvegostomig targets TIGIT and PD-1 with reduced Fc effector function. Hypothesis is that this Fc feature will allow rilvegostomig to succeed where tiragolumab (by Roche), an Fc-active MAb, failed. However, correctness of this hypothesis is now not strong given failure of domvanalimab, an Fc-silent molecule.
TIGIT programs certainly show importance of early critical evaluation for probability of success before large Phase III programs are implemented.”