A Phase 1 Study of PF-07062119, an Anti-GUCY2C/Anti-CD3 Bispecific Fc Antibody, in Patients With Advanced Gastrointestinal Cancers

PURPOSE: PF-07062119 is an anti-GUCY2C/anti-CD3ε bispecific Fc antibody designed to elicit systemic anti-tumor immunity. This phase 1, first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, immunogenicity, and anti-tumor activity of PF-07062119 as monotherapy and in combination with sasanlimab or bevacizumab in patients with advanced gastrointestinal cancers expressing GUCY2C. PATIENTS AND METHODS: Patients received escalating doses of PF-07062119 (45-3700 μg subcutaneously [SC]) in Part 1A. In Part 1B, PF-07062119 was administered with either sasanlimab (300 mg SC) or bevacizumab (5 mg/kg intravenously). Primary endpoints were safety and tolerability; secondary endpoints included PK, immunogenicity and efficacy. RESULTS: A total of 79 patients were enrolled. In Part 1A, maximum tolerated dose without a priming dose was 800 μg. Dose-limiting toxicities observed at this level were grade 3 cytokine release syndrome (CRS), colitis, and diarrhea. A 400 μg priming dose with premedication reduced CRS incidence and recommended dose for expansion was 2100 μg. Treatment-related grade 3/4 treatment-emergent adverse events (TEAEs) were observed in 27 (34.2%) patients, with no grade 5 treatment-related TEAEs. Diarrhea remained the most clinically significant toxicity in Part 1A. Combination therapy in Part 1B did not result in significant additional toxicity. PK analyses demonstrated dose-proportional increases in exposure. The overall response rate was 2.5% across all cohorts. CONCLUSIONS: PF-07062119 monotherapy demonstrated a generally tolerable safety profile within the context of this early-phase study with evidence of clinical activity in patients with advanced/metastatic gastrointestinal cancers. CLINICAL TRIAL INFORMATION: NCT04171141.