Targeting FGFR3 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, 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.
Keywords: FGFR inhibitor; FGFR3; PROOF 302; adjuvant cisplatin-based chemotherapy; adjuvant therapy; cisplatin-therapy refusal; fusions or rearrangements; infigratinib; muscle-invasive urothelial carcinoma; mutations; neoadjuvant cisplatin-based chemotherapy; phase III; upper tract urothelial carcinoma; urothelial bladder carcinoma; urothelial carcinoma.
Source: PubMed