Phase 2 FORAY tests selective FGFR3 inhibition with vepugratinib in low-grade bladder and upper tract urothelial tumors

FORAY is an Eli Lilly/Loxo Oncology Phase 2, randomized, open-label study of oral vepugratinib (LOXO-435; LY3866288), an isoform-selective FGFR3 tyrosine kinase inhibitor. Its two disease settings are low-grade, intermediate-risk non-muscle-invasive bladder cancer with an FGFR3 mutation or fusion and low-grade upper tract urothelial carcinoma. Eligibility and treatment assignment are cohort-specific rather than interchangeable between bladder and upper tract disease.

The study assesses tumor control and safety while exploring an earlier use of FGFR3-directed therapy than treatment of advanced metastatic disease. Low-grade urothelial tumors can require repeated endoscopic procedures and long-term surveillance despite relatively favorable biology. Existing management includes transurethral resection and intravesical treatment for appropriate bladder tumors, and selected kidney-sparing procedures or other local treatment for upper tract disease. The clinical question is whether systemic FGFR3 inhibition can reduce disease or procedure burden sufficiently to justify systemic treatment and its toxicities in this lower-grade population.