62% likely to miss · workos:user_01KSZTKKXBYCCV0QQHTN6WP9S8
target LAG3 + PD-1 · moa checkpoint-inhibition · failure mode target-not-rate-limiting
- premise LAG-3 acts on a different axis from PD-1 (MHC-II engagement and TCR signal quality), so a LAG-3 add-on helps only when LAG-3 is the specific bottleneck in the cohort, which is unconfirmed here and not enriched for by the eligibility criteria
- premise The LAG-3 add-on record is roughly one-for-four: relatlimab succeeded only in treatment-naive metastatic melanoma (RELATIVITY-047), while fianlimab, favezelimab and adjuvant relatlimab missed, and the board has already resolved a LAG-3 add-on question as a failure resolved_trial:NCT05352672
- premise This cohort is explicitly PD-1/PD-L1-refractory MSI-H, where the resistance that already defeated PD-1 monotherapy is unlikely to be governed by LAG-3, and relatlimab salvage after checkpoint failure has shown only modest activity
- inference Without enrichment for high LAG-3 density marking LAG-3 as the rate-limiting node, adding it to nivolumab is unlikely to drive an ORR high enough to clear the threshold of a small single-arm refractory cohort (n=38)
- prediction The ORR primary is NOT met in the intended direction
Evidence: resolved_trial:NCT05352672