A Phase 1, Multicenter, Dose-Escalation Study Of Prn1371, An Irreversible Covalent Fgfr1-4 Kinase Inhibitor, In Patients With Advanced Solid Tumors, Followed By Expansion Cohorts In Patients With Fgfr Genetic Alterations.

TPS2602Background: FGFR inhibition is a promising therapeutic approach in a number of solid tumors where genetic alterations of FGFR drive tumor cell proliferation, and survival. PRN1371 is an oral, potent, irreversible inhibitor of FGFR1-4 that has shown high potency against many FGFR-aberrant cell lines. Methods: Part A of this phase 1 clinical trial explores ascending doses of PRN1371 in adult patients with advanced solid tumors in a + 3 design, where cohorts of three patients are studied at each level until additional patients need to be added to better assess safety, establish the maximum tolerated dose and define the recommended phase 2 dose (RP2D). PRN1371 is dosed once daily in continuous, 28-day cycles. Part B studies two or three cohorts of 10 patients each with FGFR1-4 gene mutations, fusions, or truncations at the RP2D. The on-target effect of serum phosphorus and FGF23 increases are measured as potential pharmacodynamic biomarkers. Elevated serum phosphorus is managed with oral phosphate ...