A multicenter, open-label, phase I/II study of FN-1501 in patients with advanced solid tumors and acute myeloid leukemia.
Authors: Al-Rajabi Raed Moh'd Taiseer , Richardson Gary Edward , Uprety Dipesh , Williamson Stephen K. , Hamid Anis , Baranda Joaquina Celebre , Mamdani Hirva , Lee Yali , Li Chao , . Nitika , Wei Jiao , Hui Ai-Min 
Published: June 2022

e15083 Background: FN-1501, a potent inhibitor of receptor FMS-like tyrosine kinase 3 (FLT3) and CDK4/6, KIT, PDGFR, VEGFR2, ALK and RET tyrosine kinase proteins, has demonstrated significant in vivo anti-tumor activity in a broad range of solid tumor and leukemia xenograft models. FLT3 mutations have an established role as a therapeutic target in Acute Myeloid Leukemia (AML), where the gene plays a critical role in the growth, differentiation, and survival of hematopoietic cells. An open-label, Phase I/II study ( NCT03690154 ) is evaluating the safety and PK profile of FN-1501 as monotherapy in patients (pts) with advanced solid tumors and relapsed, refractory (R/R) AML. Methods: Pts received FN-1501 IV thrice weekly for 2 weeks followed by 1 week off treatment in 21-day cycles. Dose escalation follows a 3+3 design. Primary objectives include determination of maximum tolerated dose (MTD), safety, and recommended phase 2 dose (RP2D). Secondary objectives include pharmacokinetics (PK) and preliminary anti-tumor activity. Exploratory objectives include the relationship between pharmacogenetic mutations (e.g., FLT3, TP53, KRAS, NRAS), safety, efficacy and pharmacodynamic effects of FN-1501. Dose expansion at RP2D was designed to further explore safety and efficacy. Results: As of Dec 3, 2021 data cut-off (DCO), 47 pts with advanced solid tumors (N = 46) or AML (N = 1) were enrolled at doses ranging from 2.5 to 226 mg. The median age was 65 (range 30-92) with 57% female and 43% male. The median prior lines of treatment were 5 (range 1-12). Forty pts with median exposure of 9.5 cycles (range 1-18 cycles) were evaluable for dose limiting toxicity (DLT). Treatment-related adverse events (TRAEs) were reported in 64% of pts. The most common treatment-emergent adverse events (TEAEs) defined as those occurring in ≥ 20% of patients primarily consisted of reversible grade 1-2 fatigue (34%), nausea (32%) and diarrhea (26%). The most common grade ≥ 3 events occurring in ≥ 5% of pts consisted of diarrhea and hyponatremia. Dose escalation was discontinued due to DLTs of grade 3 thrombocytopenia (N = 1) and grade 3 infusion related reaction (N = 1) in 2 pts in the 226 mg dose group (2nd DLT reported after DCO). At the time of DCO, 33 pts were evaluable for disease response showing 1 with partial response (PR) (47% target lesion shrinkage), 15 with stable disease (SD) and 17 with progression of disease (PD). The PR lasted > 4 months (mts) in a patient with endometrial carcinoma (ca) at the 40 mg dose level. The longest treatment exposures were recorded in 6 pts with SD of 2.6 to > 12 mts (thymoma [1]; ovarian ca [2]; renal cell ca [1]; laryngeal ca [1] and intestinal adeno ca [1]) at doses ranging from 15 mg to 170 mg. Conclusions: FN-1501 IV has shown reasonable safety, tolerability, and preliminary activity against solid tumors up to 170 mg. Dose escalation was terminated based on 2 DLTs occurring at the 226 mg dose level. Clinical trial information: NCT03690154.