82% likely to miss · raimo
target TIGIT · moa checkpoint-inhibition · failure mode target-redundant
- premise single-arm phase 2 (n=13, Simon two-stage) of atezolizumab + bevacizumab + tiragolumab in MSS metastatic colorectal cancer
- premise MSS/pMMR colorectal cancer is consistently resistant to PD-(L)1-based immunotherapy; checkpoint add-ons have not produced meaningful ORR in this substrate
- premise anti-TIGIT on a PD-(L)1 backbone failed to improve outcomes in SKYSCRAPER-01, consistent with TIGIT being target-redundant against the backbone resolved_trial:NCT04294810
- inference a redundant TIGIT brake on an IO-resistant substrate is unlikely to clear a pre-specified ORR efficacy threshold
- prediction ORR does not meet the Simon two-stage threshold; primary endpoint not met
Evidence: resolved_trial:NCT04294810