Clinical and LAT1 Biomarker Correlates of Clinical Benefit from Nanvuranlat (JPH203) in Advanced Biliary Tract...

Background/Objectives: This exploratory post hoc analysis evaluated clinical and biomarker-defined treatment effects and accumulated nanvuranlat exposure in advanced biliary tract cancer (BTC). Methods: BICR-assessed progression-free survival (PFS) and overall survival (OS) were analyzed in the randomized Phase 2 full analysis set of 104 patients (nanvuranlat, n = 69; placebo, n = 35). Formal treatment-by-subgroup interaction tests assessed prior primary tumor resection status, LAT1 expression, and anatomical BTC subtype, evaluated both as a four-category variable and as pooled IHC/EHC/GBC versus AVC. Accumulated-exposure analyses pooled Phase 1 and Phase 2 data and were descriptive. Results: Median PFS was 46 versus 43 days (HR, 0.557; 95% CI, 0.344-0.903), and median OS was 155 versus 144 days (HR, 0.875; 95% CI, 0.551-1.390). Interaction tests were nominally significant for resection status with OS (p = 0.028) and for the four-category BTC-subtype variable with PFS (global p = 0.035), but not for LAT1 expression (PFS, p = 0.157; OS, p = 0.586) or pooled IHC/EHC/GBC versus AVC (PFS, p = 0.511; OS, p = 0.208). The binary and four-category subtype analyses addressed different hypotheses and were not considered contradictory. Higher accumulated-exposure quartiles showed numerically longer survival, but these analyses were susceptible to immortal-time bias, reverse causation, and time-dependent confounding. Conclusions: Nanvuranlat was associated with a lower hazard of progression or death than placebo, whereas the OS estimate was less conclusive. The subgroup and exposure findings remain exploratory but support prospective evaluation of resection status, anatomical subtype, and LAT1 expression.