A Phase I Study of PF-07062119, an Anti-GUCY2C/Anti-CD3 Bispecific Fc Antibody, in Patients with Advanced Gastrointestinal Cancers
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: PURPOSE: PF-07062119 is an anti-GUCY2C/anti-CD3ε bispecific Fc antibody designed to elicit systemic antitumor immunity. This phase I, first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor activity of PF-07062119 as monotherapy and in combination with sasanlimab or bevacizumab in patients with advanced gastrointestinal (GI) cancers expressing GUCY2C. PATIENTS AND METHODS: Patients received escalating doses of PF-07062119 (45-3,700 μg SC) in part 1A. In part 1B, PF-07062119 was administered with either sasanlimab (300 mg SC) or bevacizumab (5 mg/kg i.v.). 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 2,100 μg. Treatment-related grade 3/4 treatment-emergent adverse events (TEAE) 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 GI cancers. SIGNIFICANCE: GUCY2C is universally expressed in colorectal cancer and ectopically expressed by other GI cancers. In this first-in-human phase I study, PF-07062119, an anti-GUCY2C/anti-CD3ε bispecific Fc antibody, demonstrated a generally tolerable safety profile with evidence of antitumor activity in patients with advanced GI cancers.
Source: Cancer Research Communications
Authors: Marwan Fakih, Toshihiko Doi, Anthony Tolcher, David Hong, Jeanne Tie, Wells Messersmith, Takafumi Koyama, Lee Rosen, Joana Borlido, Michael A. Damore, Maria Delioukina, Ioanna Cheronis, Lee Noel Clark, Marzieh Golmakani, Amy Jackson-Fisher, Szu-Yu Tang, Cathy Cen Guo, Edmund J. Keliher, Kevin Maresca, Neil H. Segal
Institutions: City Of Hope National Medical Center, City of Hope, National Cancer Center Hospital East, The University of Texas MD Anderson Cancer Center, Peter MacCallum Cancer Centre, University of Colorado Denver, National Cancer Center Hospital, UCLA Medical Center, Pfizer (United States), Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,550
OpenAlex ID: W7208764894