Antitumor activity and safety of FPA144, an ADCC-enhanced, FGFR2b isoform-selective monoclonal antibody, in patients with FGFR2b+ gastric cancer and advanced solid tumors.

2502 Background: FGFR2b-overexpressing gastric cancer is a distinct setting with poor prognosis. FPA144, a humanized monoclonal IgG1 antibody directed against FGFR2b, has been engineered for enhanced ADCC and specific FGFR2 signaling blockade. FPA144-001 is a two-part first-in-human Phase 1 study of FPA144 monotherapy: Part 1 dose escalation in patients with advanced solid tumors (Part 1A) and advanced gastric cancer (Part 1B); and Part 2 expansion to evaluate the safety, PK and early efficacy in selected gastric cancer patients treated at the recommended dose (RD). Methods: Part 1A was a 3+3 design to assess safety and PK of FPA144 and to establish a RD. Patients with gastric cancer were enrolled in parallel Part 1B cohorts to provide gastric cancer PK. Part 2 eligibility requires a diagnosis of gastric cancer and tissue for FGFR2b expression analysis. Tumor testing is done centrally using a proprietary FGFR2b-selective IHC assay. Results: Part 1 of the study enrolled 27 patients – 19 in Part 1A and 8 in Part 1B, including 6 patients with FGFR2b-overexpressing gastric cancer tumors in Part 1B. No DLTs, treatment-related SAEs or treatment delays were observed during dose escalation; 15mg/kg q2w is the dose being explored in Part 2. Fatigue and decreased appetite were the most common treatment-related AEs. In Part 1A, a patient with recurrent bladder cancer treated at 3mg/kg had radiographic and metabolic disappearance of lesions by day 50. Of 6 FGFR2b-overexpressing gastric cancer patients in Part 1B, 2 achieved PRs (1 confirmed, 1 unconfirmed at time of analysis) and 3 demonstrated SD as best response (2 confirmed, 1 unconfirmed). Initial PK analysis demonstrates that FPA144 exposure in subjects with gastric cancer is similar to that in other solid malignancies. Updated safety, PK, and efficacy data will be presented. Conclusions: FPA144, an afucosylated monoclonal antibody directed against FGFR2b, has a well-tolerated safety profile: no DLTs in dose escalation and no treatment-related SAEs to date. Early evidence of single-agent anti-tumor effect in patients with FGFR2b-overexpressing gastric cancer and bladder cancer has been observed. Clinical trial information: NCT02318329.