Pemigatinib for metastatic or surgically unresectable urothelial carcinoma with FGF/FGFR genomic alterations: final results from FIGHT-201

Background Fibroblast growth factor receptor 3 (FGFR3) alterations are oncogenic drivers of urothelial carcinoma (UC). Pemigatinib is a selective, oral inhibitor of FGFR1-3 with antitumor activity. We report the efficacy and safety of pemigatinib in the open-label, single-arm, phase II study of previously treated, unresectable or metastatic UC with FGFR3 alterations (FIGHT-201; NCT02872714). Patients and methods Patients >= 18 years old with FGFR3 mutations or fusions/rearrangements (cohort A) and other FGF/FGFR alterations (cohort B) were included. Patients received pemigatinib 13.5 mg once daily continuously (CD) or intermittently (ID) until disease progression or unacceptable toxicity. The primary endpoint was centrally confirmed objective response rate (ORR) as per RECIST v1.1 in cohort A-CD. Secondary endpoints included ORR in cohorts A-ID and B, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results Overall, 260 patients were enrolled and treated (A-CD, n = 101; A-ID, n = 103; B, n = 44; unconfirmed FGF/FGFR status, n = 12). All discontinued treatment, most commonly due to progressive disease (68.5%). ORR [95% confidence interval (CI)] in cohorts A-CD and A-ID was 17.8% (10.9% to 26.7%) and 23.3% (15.5% to 32.7%), respectively. Among patients with the most common FGFR3 mutation (S249C; n = 107), ORR was similar between cohorts (A-CD, 23.9%; A-ID, 24.6%). In cohorts A-CD/A-ID, median (95% CI) DOR was 6.2 (4.1-8.3)/6.2 (4.6-8.0) months, PFS was 4.0 (3.5-4.2)/4.3 (3.9-6.1) months, and OS was 6.8 (5.3-9.1)/8.9 (7.5-15.2) months. Pemigatinib had limited clinical activity among patients in cohort B. Of 36 patients with samples available at progression, 6 patients had 8 acquired FGFR3 secondary resistance mutations (V555M/L, n = 3; V553M, n = 1; N540K/S, n = 2; M528I, n = 2). The most common treatment-emergent adverse events overall were diarrhea (44.6%) and alopecia, stomatitis, and hyperphosphatemia (42.7% each). Conclusions Pemigatinib was generally well tolerated and demonstrated clinical activity in previously treated, unresectable or metastatic UC with FGFR3 mutations or fusions/rearrangements.