Abstract A077: FIGHT-207: Phase 2 study of pemigatinib in patients with previously treated, locally advanced/metastatic or unresectable solid tumor malignancies harboring activating fibroblast growth factor receptor (FGFR) gene alterations

Introduction: Activating mutations, rearrangements, and amplifications of FGFR, resulting in either ligand-independent or aberrant ligand-dependent FGFR signaling have been identified in many tumor types. A recent large-scale sequencing study across tumor types identified FGFR alterations in 7.1% of cancers, including gene amplification (66%), mutations (26%), and rearrangements (8%) (Helsten CCR 2016). Pemigatinib (INCB054828) is a selective, potent, oral inhibitor of FGFR1–3 that has demonstrated antitumor activity in FGFR-driven tumors in phase 1/2 (FIGHT-101) and phase 2 (FIGHT-201, -202, and -203) studies. FIGHT-207 is a phase 2, open-label, single-arm, tumor-agnostic study that will evaluate the efficacy and safety of pemigatinib monotherapy in patients with advanced/metastatic or surgically unresectable solid tumor malignancies with activating FGFR mutations, fusions or rearrangements (NCT03822117). Methods: Eligible patients (aged ≥18 years) have histologically or cytologically confirmed solid tumor malignancy that is advanced/metastatic or is surgically unresectable; radiographically measurable disease (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1] or Response Assessment in Neuro-Oncology [RANO] for primary brain tumors); documented FGFR1–3 mutation or translocation; objective progression after at least 1 prior therapy, and no therapy available that is likely to provide clinical benefit; Eastern Cooperative Oncology Group performance status 0 to 2; and no prior receipt of a selective FGFR inhibitor. Patients are assigned to 1 of 3 cohorts based on FGFR status: Cohort A (n ~ 60): FGFR1–3 in-frame fusions or FGFR2 intron 17 rearrangements; Cohort B (n ~ 90): known/predicted activating point mutations in FGFR1–3; and Cohort C (n ~ 20): any FGFR1–3 point mutations in the kinase domain, variants of unknown significance or FGFR1/FGFR3 rearrangements without an identified partner gene. All patients receive a starting dose of pemigatinib 13.5 mg once daily on a 21-day cycle. Patients with no grade ≥2 treatment-related adverse events and no hyperphosphatemia (serum phosphate >5.5 mg/dL) during cycle 1 are allowed to increase dose to pemigatinib 18 mg from cycle 2. Treatment continues as long as patients are receiving benefit or until treatment withdrawal criteria are met. Hyperphosphatemia is managed with diet modifications, phosphate binders, and diuretics, or pemigatinib dose reduction/interruption. The primary endpoint is objective response rate (assessed by independent review committee [IRC] per RECIST v1.1 or RANO) in Cohorts A and B. Secondary endpoints are progression-free survival, duration of response, and overall survival in Cohorts A and B; safety and tolerability in all cohorts. Biopsies will be obtained for select tumors at screening, on-treatment, and at end of treatment. Additional biomarkers that may be indicative of clinical response, resistance, and safety may also be investigated. The study is currently recruiting. Citation Format: Luis Feliz, Ekaterine Asatiani, Christine Lihou, Huiling Zhen, Ian Silverman, Jordi Rodon Ahnert. FIGHT-207: Phase 2 study of pemigatinib in patients with previously treated, locally advanced/metastatic or unresectable solid tumor malignancies harboring activating fibroblast growth factor receptor (FGFR) gene alterations [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 A077. doi:10.1158/1535-7163.TARG-19-A077