FPA144-001: A first in human study of FPA 144, an ADCC-enhanced, FGFR2b isoform-selective monoclonal antibody in patients with advanced solid tumors.

140 Background: FPA144 is a humanized monoclonal IgG1 antibody directed against the 2b Isoform of thefibroblast growth factor receptor (FGFR2b) that has been glycoengineered to enhance ADCC. Amplification of FGFR2 is found in a number of tumors, including 3 – 9% of gastric cancer, and is associated with poor prognosis. FPA144-001 is a phase 1 study in two parts: Part 1 will evaluate the safety and pharmacokinetics (PK) of FPA144 in patients with solid tumors; Part 2 will evaluate efficacy in gastric cancer patients whose tumors overexpress FGFR2b, as determined by a proprietary test. Here we present early safety and PK results from solid tumor patients treated with FPA144. Methods: A standard 3+3 design was used to assess safety, tolerability and PK of escalating doses of FPA144 in patients with advanced solid tumors (Part 1A) or recurrent/metastatic gastric cancer (Part 1B). Tumor testing for FGFR2gene amplification or FGFR2b overexpression was conducted centrally by a proprietary assay consisting of both FISH and IHC. Results: At the time of data analysis, enrollment of FPA144-001 through the 6mg/kg q2w cohort had been completed. In Part 1A, 13 patients with 8 different tumor types have been enrolled. Patients have been treated for an average of 4 cycles (range 1 – 10, median 2) or 101 days (range 28 – 287, median 43). Nine patients have discontinued the study for progressive disease or lack of clinical benefit; all others continue on study treatment. No dose-limiting toxicities have been observed, and no patients have withdrawn due to an adverse drug reaction. Upper respiratory infection, alopecia and fatigue are the AEs reported in more than one patient; one SAE of dyspnea and pyrexia not related to drug has been reported. PK analysis demonstrates non-linear clearance in doses up to 3mg/kg, likely due to receptor-mediated clearance. Conclusions: FPA144 is a glycoengineered monoclonal antibody directed against FGFR2b that is being developed for the treatment of patients with tumors that overexpress FGFR2b. FPA144 has been safely administered at doses up to 6mg/kg q2w; dose escalation continues. Updated safety, PK and anti-tumor activity will be presented. Clinical trial information: NCT02318329.