Abstract CT527: A phase I open-label study of FGFR/VEGFR inhibitor FH-2001 in patients with advanced solid tumors
Authors: Song Zhengbo , Hui Ai-min , Wu Zhuli , Liu Huilong , Cheng Xiangdong 
Published: June 2022

Purpose: FH-2001 is a FGFR/VEGFR targeted drug that can reduce the expression level of PD-L1 in tumor cells by down-regulating the cMYC gene. The anti-tumor activity of FH-2001 has been confirmed in preclinical studies. Apart from exerting potent anti-proliferative effect on FGFR-driven tumors, FH-2001 may be able to overcome primary and secondary resistance of conventional immune checkpoint inhibitors or increase the response rate through PD-L1 regulation. This first-in-human study evaluated the safety, tolerability, pharmacokinetics and anti-tumor activity of FH-2001 in patients with advanced solid tumors.

Methods: This open-label, non-randomized, multicenter phase I study has two parts. The first part comprised a dose escalation and a dose expansion phase to evaluate the safety, tolerability and determine the maximum tolerated dose(MTD)and phase II recommended dose (RP2D) of FH-2001. The dose escalation phase enrolled patients with advanced solid tumors with planned dose levels for 1, 2, 4, 8, 12 or 16 mg. The accelerated titration design was used in the dose escalation phase for 1 and 2 mg dose, and if grade 2 or higher drug-related adverse events (TRAEs) occurred during the dose-limiting toxicity (DLT) period between cycle 0 and 1 with 25 days, dose escalation would subsequently follow the 3+3 design. All other doses utilized the 3+3 design. Patients first received a single dose of FH-2001, and if no DLT or other unacceptable occurred, patients subsequently receive FH-2001 once daily in 21-day cycles. FH-2001 at a dose where objective efficacy was observed or reached effective exposure were selected for dose expansion. In the dose expansion phase, patients with advanced solid tumors harboring FGFR gene aberrations were enrolled, with 6-12 patients at each dose level, and they received FH-2001 once-a-day continuously in 21-day cycles. RP2D was determined based on the safety, pharmacokinetic/pharmacodynamic and preliminary efficacy data that were available in the first part of the study. The second part of the study commenced after RP2D was confirmed, which is a two-cohort study to evaluate the efficacy and safety of FH-2001. The first cohort comprised patients with advanced solid tumors who had progressed on prior treatment with an immune checkpoint inhibitor. The second cohort included patients with locally advanced or metastatic solid tumors with FGFR gene aberrations. Approximately 30 patients were enrolled in each cohort. Safety was assessed throughout the study and for 30 days after the last dose. Tumor response was assessed by the investigators according to RECIST v1.1. Pharmacokinetics and pharmacodynamics were evaluated at prespecified time points.

Citation Format: Zhengbo Song, Ai-min Hui, Zhuli Wu, Huilong Liu, Xiangdong Cheng. A phase I open-label study of FGFR/VEGFR inhibitor FH-2001 in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT527.