Targeting <i>FGFR3</i> Alterations with Adjuvant Infigratinib in Invasive Urothelial Carcinoma: the Phase III PROOF 302 Trial
Sumanta K. Pal, Diederik M. Somford, Petros Grivas, Srikala S. Sridhar, Shilpa Gupta, Joaquim Bellmunt, Guru Sonpavde, Mark T. Fleming, Seth P. Lerner, Yohann Loriot, Jean Hoffman‐Censits, Begoña P. Valderrama, Corina Andresen, Marco J. Schnabel, Suzanne Cole, Siamak Daneshmand
Abstract
PROOF 302 is an ongoing randomized, double-blind, placebo-controlled, adjuvant phase III trial (NCT04197986) in approximately 218 patients from 120 centers worldwide. Eligibility criteria include post-surgical high-risk muscle-invasive upper tract urothelial cancer (85% of patients) or urothelial bladder cancer (15%), susceptible FGFR3 alterations (activating mutations, gene fusions or rearrangements), ≤120 days following radical surgery and ineligible for/or refusing cisplatin-based (neo)adjuvant chemotherapy. Patients receive either oral infigratinib 125 mg or placebo daily on days 1–21 of a 28-day cycle for up to 52 weeks or until recurrence, unacceptable toxicity or death. Primary end point: centrally determined disease-free survival (DFS); secondary end points: investigator-assessed DFS, metastasis-free survival, overall survival and safety/tolerability; exploratory end points: correlative biomarker analysis, quality-of-life and infigratinib pharmacokinetics.