Abstract A078: FIGHT-101: A phase 1/2 study of pemigatinib, a highly selective fibroblast growth factor receptor (FGFR) inhibitor, as monotherapy and as combination therapy in patients with advanced malignancies
Authors: Subbiah Vivek , Barve Minal , Iannotti Nicholas O. , Gutierrez Martin , Smith David C. , Roychowdhury Sameek , Papadopoulos Kyriakos P. , Mettu Niharika , Edenfield William J. , Morgensztern Daniel , Féliz Luis , Lihou Christine , Zhen Huiling , Saleh Mansoor 
Published: March 2020

Abstract
Background: FGFR pathway activation is implicated in many solid tumors. Pemigatinib (INCB054828) is a selective FGFR1–3 inhibitor. We report updated data from FIGHT-101 (NCT02393248), a phase 1/2 study of pemigatinib alone, and combined with other agents, in patients with refractory advanced malignancies progressing after prior therapy, with no further effective standard therapy available. Methods: Eligible adults had advanced malignancies with/without FGF/FGFR alteration. Patients received oral pemigatinib QD on intermittent dosing (ID) 21-day (14-day-on/7-day-off) cycle or continuous dosing (CD) schedules. In part 1 (FGF/FGFR alteration not required), cohorts 1–3 (1–4 mg QD) evaluated single patients; escalation followed a 3+3 design (6–20 mg QD). In part 2 (dose expansion; documented FGF/FGFR alteration required), initial patients were dosed with pemigatinib 9 mg QD; additional patients were dosed at 13.5 mg and 20 mg QD. In part 3, pemigatinib was combined with standard therapies (dose-finding and expansion). Results: At data cutoff (February 19, 2019), 45, 71, and 44 patients were enrolled in parts 1–3, respectively. No dose-limiting toxicities were observed with monotherapy. Maximum tolerated dose was not reached, the pharmacologically active dose was 9 mg QD; the maximum safely administered dose was 20 mg. Recommended phase 2 dose was 13.5 mg QD, based on PK, pharmacodynamics, and safety. In parts 1 and 2 (n=116; median age, 58 y [range, 21–77]; men, 39%), 103 (89%) discontinued therapy (progressive disease [PD], 54%). In part 3 (n=44), 39 (89%) discontinued therapy (PD, 55%). Of 117 patients evaluated for FGF/FGFR status in parts 1–3, 100 (85%) had FGF/FGFR alterations. In parts 1 and 2, the most frequent all-cause, all-grade (Gr) adverse events (AEs) for ID were hyperphosphatemia (74%) and fatigue (40%) for 9 mg/13.5 mg doses (n=57); and hyperphosphatemia (67%) and stomatitis (50%) for the 20 mg dose (n=6); for CD, hyperphosphatemia (73%) and stomatitis (48%) for 9 mg/13.5 mg doses (n=33); and hyperphosphatemia (69%), dry mouth and diarrhea (each, 54%) for the 20 mg dose (n=13). The most frequent Gr ≥3 AEs across all dose levels in parts 1 and 2 for ID (n=70) were hyponatremia and pneumonia (each, 7%); for CD (n=46), fatigue (13%). In part 3, the most frequent all-cause, all-Gr AEs were anemia (73%) for pemigatinib + chemotherapy (gemcitabine + cisplatin/docetaxel; n=15); hyperphosphatemia and alopecia (each, 83%) for pemigatinib + trastuzumab (n=6); and hyperphosphatemia (74%) for pemigatinib + pembrolizumab (n=23). Most frequent Gr ≥3 AEs were neutropenia (40%) for pemigatinib + chemotherapy; diastolic hypertension, hypophosphatemia, lymphopenia, and portal vein thrombosis (each, 17%) for pemigatinib + trastuzumab; and anemia and diarrhea (each, 13%) for pemigatinib + pembrolizumab. In parts 1–3, hyperphosphatemia was managed with phosphate binders, diet and/or dose reduction (n=2) or delay (n=8). Conclusions: Pemigatinib was generally well tolerated as monotherapy and as combination therapy in patients with advanced malignancies and FGFR pathway activation. Updated data including efficacy data will be presented. Rapid development including a basket trial is planned.
Citation Format: Vivek Subbiah, Minal Barve, Nicholas O. Iannotti, Martin Gutierrez, David C. Smith, Sameek Roychowdhury, Kyriakos P. Papadopoulos, Niharika Mettu, William J. Edenfield, Daniel Morgensztern, Luis Féliz, Christine Lihou, Huiling Zhen, Mansoor Saleh. FIGHT-101: A phase 1/2 study of pemigatinib, a highly selective fibroblast growth factor receptor (FGFR) inhibitor, as monotherapy and as combination therapy in patients with advanced malignancies [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A078. doi:10.1158/1535-7163.TARG-19-A078