Preliminary results from fight-102: a phase 1 study of pemigatinib in Japanese patients with advanced malignancies

Abstract

Abstract Background Dysregulated fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling resulting from oncogenic FGFR alterations is implicated in many cancers. Pemigatinib (INCB054828) is an oral, selective FGFR1, 2, and 3 inhibitor. This phase 1, multisite, open-label study evaluated pemigatinib in Japanese patients (pts) with advanced malignancies (NCT03235570). Methods Japanese pts (≥20 y) in part 1 (dose escalation) had advanced solid tumors and no standard therapies available. Pts in part 2 (dose expansion) had measurable disease with FGF/FGFR alterations. Part 1 pts were enrolled using a 3 + 3 design to receive pemigatinib starting at 9 mg QD and then at 13.5 mg QD, each on 21-d 2-wk on/1-wk off intermittent dosing cycles. Part 2 pts started at the recommended phase 2 dose (RP2D). Primary endpoint was safety. Results As of the data cutoff (January 18, 2019), 25 pts were enrolled (part 1, n = 9; part 2, n = 16). Median age was 63 (range, 32-79) y; 16 pts were men; 24 pts discontinued therapy, mainly due to disease progression (n = 21). Most common tumors were esophageal (n = 5) and cholangiocarcinoma (n = 3). No dose-limiting toxicities occurred; the RP2D was 13.5 mg QD (intermittent dosing). Most common adverse events (AEs) were hyperphosphatemia (n = 19), dysgeusia (n = 9), alopecia (n = 8), constipation, diarrhea, nausea, and decreased appetite (each, n = 7); most frequent grade ≥3 AEs were anemia, cholangitis, and decreased appetite (each, n = 2). One pt with metastatic adenocarcinoma and FGFR2 amplification had a partial response (ongoing at cutoff); 9 pts had stable disease. At 13.5 mg, steady-state geometric mean (%CV) maximum concentration was 159 nmol/L (88.5%), area under the curve was 2300 h·nmol/L (58.5%), and terminal half-life was 14.0 h (42.1%). Conclusions In these Japanese pts with advanced malignancies, the pemigatinib tolerability profile is consistent with previous reports; pharmacokinetics are similar to Western populations. Recruitment is ongoing.