Cancer research communications · 2026
A Phase 1 Study of PF-07062119, an Anti-GUCY2C/Anti-CD3 Bispecific Fc Antibody, in Patients With Advanced Gastrointestinal Cancers.
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Fakih Marwan, Doi Toshihiko, Tolcher Anthony, Hong David, Tie Jeanne, Messersmith Wells, Koyama Takafumi, Rosen Lee, Borlido Joana, Damore Michael A, Delioukina Maria, Cheronis Ioanna, Clark Lee Noel, Golmakani Marzieh, Jackson-Fisher Amy, Tang Szu-Yu, Guo Cathy C, Keliher Edmund J, Maresca Kevin, Segal Neil H
Аннотация
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.
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.