CTNI-39. FIGHT-209: A PHASE 2, OPEN-LABEL, MULTICENTER STUDY OF PEMIGATINIB IN PATIENTS WITH PREVIOUSLY TREATED GLIOBLASTOMA OR OTHER PRIMARY CENTRAL NERVOUS SYSTEM TUMORS WITH ACTIVATING FGFR1-3 ALTERATIONS

Abstract

Abstract Fibroblast growth factor receptor (FGFR) signaling plays a role in progression of gliomas. Pemigatinib is a potent selective inhibitor of FGFR1-3, with demonstrated antitumor activity in patients with cholangiocarcinoma harboring FGFR2 fusions/rearrangements. The FIGHT-209 study will evaluate pemigatinib treatment for patients with glioblastoma or other primary central nervous system tumors harboring activating FGFR mutations or fusions/rearrangements. Eligible patients are adults with a radiologically measurable and histologically or molecularly confirmed recurrent glioblastoma, other diffuse glioma, or circumscribed astrocytic tumors harboring a FGFR1-3 gene alteration or fusion/rearrangement. Patients must have Karnofsky performance status ≥ 60, life expectancy ≥ 12 weeks, and documented disease progression after prior therapy with no available therapy likely to provide clinical benefit. Exclusion criteria include prior treatment with FGFR or VEGF/VEGFR inhibitors (other than bevacizumab for radiation necrosis), evidence of corneal or retinal disorder, or history of calcium or phosphate homeostasis disorder. Patients will be assigned to 1 of 3 cohorts based on genomic testing: A: glioblastoma with FGFR1-3 fusions/rearrangements; B: other CNS tumors with FGFR1-3 fusions/rearrangements; C: glioblastoma or other CNS tumors with FGFR1-3 activating mutations. Patients will receive pemigatinib 13.5 mg administered orally QD on a 21-day treatment cycle (2 weeks on/1 week off). Hyperphosphatemia, an on-target pharmacologic effect of FGFR inhibition, will be managed with diet modification, phosphate binders, diuretics, or dose reduction. Treatment will continue until disease progression or unacceptable toxicity. Primary endpoints are objective response rate (ORR) in cohorts A and B based on response assessment in neuro-oncology and assessed by ICR. Secondary endpoints include ORRs in cohorts A and B combined, in all cohorts, and in cohort C alone and the following endpoints for cohorts A and B individually: disease control rate, progression-free survival, duration of response, and overall survival. Safety and tolerability will also be assessed. Clinical trial information: NCT05267106