A phase I clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of FN-1501 monotherapy in patients with advanced solid tumors.

Abstract

TPS3150 Background: Receptor tyrosine kinases (RTK), a group of transmembrane proteins, are responsible for growth factor signaling transduction in normal cellular functions. Abnormal RTK functions are associated with human tumorigenesis. FMS-like tyrosine kinase 3 (FLT3) belongs to the type III receptor tyrosine kinase family and plays a well-established role in normal growth and differentiation of hematopoietic precursor cells. FLT3 mutations have been reported to occur in approximately 30% newly diagnosed AML patients. The internal tandem duplications mutation (FLT3/ITD) is the major mutation and correlated with more aggressive progress and poor prognosis. FN-1501 is an inhibitor of various tyrosine kinases such as cyclin-dependent kinase 4/6(CDK4/6), platelet-derived growth factor receptor (PDGFR), KIT protein, anaplastic lymphoma kinase (ALK) and RET protein, particularly potent on FLT3. The preclinical data generated from biochemical, cell based and animal in vivo studies suggest that FN-1501 as a single agent could offer cancer patients clinical benefit by inhibiting multiple tyrosine kinases including FLT3, PDGFR, KIT, ALK, and RET. Methods: This is a Phase1, open label, multicenter, dose-escalation study that will evaluate the safety, pharmacokinetics (PK), and preliminary efficacy of FN-1501 in up to 33 cancer patients with solid tumors. There is a dose escalation phase that will be followed by an expansion cohort. The dose escalation phase utilizes a standard “3 + 3” design where doses of FN-1501 will be escalated up to the Maximum-Tolerated Dose (MTD) or until the Recommended Phase 2 dose (RP2D) is identified. Once the MTD or RP2D dose is identified, an expansion cohort including patients with hematologic malignancies will be enrolled to further evaluate the safety and efficacy of FN-1501. Key exploratory analyses will include an evaluation of safety and efficacy and levels of expression and/or amplification of FLT3 mutations. As of February 8, 2019, cohorts 1 and 2 have been completed without a dose limiting toxicity (DLT). A total of 11 patients have been treated. Enrollment to cohort 3 is on-going. Clinical trial information: NCT03690154.