Interim results of fight-201, a phase II, open-label, multicenter study of INCB054828 in patients (pts) with metastatic or surgically unresectable urothelial carcinoma (UC) harboring fibroblast growth factor (FGF)/FGF receptor (FGFR) genetic alterations (GA)

Background: FGFR3 GA are implicated in the pathogenesis of UC; ≈ 15% of pts with advanced UC have mutations and 6% have translocations. INCB054828, a selective, potent, oral inhibitor of FGFR1, 2, and 3, has shown efficacy in pts with FGF/FGFR GA tumors. Methods: This study (NCT02872714) is enrolling pts with metastatic or unresectable UC who failed ≥ 1 therapy or are platinum ineligible and have FGFR3 mutations/fusions (cohort A, n = 100) or other FGF/FGFR GAs (cohort B, n = 40). Pts receive oral INCB054828 13.5 mg once daily on a 21-day cycle (2 wk on, 1 wk off) until disease progression or unacceptable toxicity. The primary endpoint is overall response rate (ORR) in cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints include ORR in cohort B, duration of response, progression-free survival, overall survival, and safety/tolerability. The primary objective of this interim analysis is to evaluate the efficacy and safety of INCB054828 in pts in cohort A who had ≥ 1 postbaseline tumor assessment or discontinued the study. Results: As of data cutoff (7 Feb 2018), 64 and 36 pts were enrolled in cohorts A and B, respectively. In cohort A, 84% (54/64) had ECOG PS ≤ 1, 39% (25/64) received ≥ 3 prior therapies, and 36% (23/64) had a prior PD-1/L1 inhibitor. Of 64 pts, 51 had ≥ 1 postbaseline scan or discontinued. Best overall responses in cohort A were 7 confirmed partial responses (PRs), 6 unconfirmed PRs (ongoing), and 17 stable disease (10 ongoing). ORR, including unconfirmed PRs, was 25% (95% CI, 14%–40%). In cohort B, 1 pt with FGF10 amplification had an unconfirmed PR. Common treatment-emergent adverse events (TEAEs) in all pts were diarrhea (40%), alopecia (32%), fatigue (29%), constipation (28%), and dry mouth (28%). Grade ≥ 3 TEAEs in > 5% of pts were urinary tract infections (7%) and fatigue (6%). Hyperphosphatemia (any postbaseline serum phosphate > 5.5 mg/dL) was 68% in cohort A and 64% in all pts. Conclusions: INCB054828 was generally well tolerated and showed preliminary efficacy in previously treated pts with UC and FGFR3 GA. Updated data will be presented. Clinical trial identification: NCT02872714. Editorial acknowledgement: Medical writing assistance was provided by Ann Yeung, CMPP, PhD, of Scientific Pathways, Inc, and funded by Incyte. Legal entity responsible for the study: Incyte Corporation. Funding: Incyte Corporation. Disclosure: A. Necchi: Consultancy (incl. expert testimony): Roche, Merck, AstraZeneca, Incyte, Clovis Oncology, Bioclin Therapeutics, Janssen, Bayer; Research funding: Merck, AstraZeneca; Honoraria: Roche, Merck, AstraZeneca, Incyte, Clovis Oncology, Bioclin Therapeutics, Janssen, Bayer. D. Pouessel: Consultancy (incl. expert testimony): Janssen, Astellas, Sanofi, AstraZeneca, Pfizer, Novartis; Honoraria: Janssen, Astellas, Sanofi, AstraZeneca, Pfizer; Travel and accommodation expenses: Sanofi, Astellas. R. Leibowitz-Amit: Consultancy (Includes expert testimony): Janssen, Bayer, Roche; Honoraria: Bristol-Myers Squibb, MSD; Membership on any entity's Board of Directors or advisory committees; Pfizer. A. Flechon: Honoraria: Pfizer, Novartis, Ipsen, Astellas, Sanofi, Janssen, Roche, MSD, Bristol-Myers Squibb; Travel and accommodation support: Pfizer, Novartis, Ipsen, Astellas, Sanofi, Janssen, Roche, MSD, Bristol-Myers Squibb. S. Gupta: Research support to Institution: Pfizer, Five Prime Therapeutics, Hoosier Oncology Group, Rexahn Pharmaceuticals, Incyte, Bristol-Myers Squibb, Novartis, LSK, Mirati, Merck; Personal: Spouse is equity holder of Salarius Pharmaceuticals. P. Barthelemy: Consultancy (incl. expert testimony): Bristol-Myers Squibb, Novartis, Pfizer, Roche, MSD; Honoraria: Janssen, Cilag, Sanofi, Astellas. M. Maio: Honoraria: Bristol-Myers Squibb, GlaxoSmithKline, AstraZeneca, Roche, MSD, Incyte; Served on Advisory Committees: Bristol-Myers Squibb, GlaxoSmithKline, AstraZeneca, Roche, MSD, Incyte. E. Asatiani, G. Serbest: Employment: Incyte; Equity Ownership: Incyte. H. Zhen: Employment: Incyte; Equity ownership: Incyte stock. Y. Loriot: Consultancy (incl. expert testimony): Seattle Genetics, Astellas, Roche, AstraZeneca, MSD, Bristol-Myers Squibb; Research funding: Sanofi, Janssen; Honoraria: Sanofi, Pfizer. All other authors have declared no conflicts of interest.