A Phase I Study of PF-07062119, an Anti-GUCY2C/Anti-CD3 Bispecific Fc Antibody, in Patients with Advanced Gastrointestinal Cancers
TL;DR
In this phase I, first-in-human phase I study, 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.
Abstract
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.