Phase I Clinical Trial of the Bifunctional EGFR/TGF-β Fusion Protein Ficerafusp Alfa (BCA101) Alone and in Combination with Pembrolizumab for Advanced Solid Tumors

作者：Alberto Hernando‐Calvo, Richard D. Carvajal, Paul K. Paik, Van Karlyle Morris, Dan Paul Zandberg, John M. Kaczmar, David N. Bohr, Ralf D. Reiners, Elham Gharakhani, Rachel L. Salazar, Patrick Hall Lizotte, Elena V. Ivanova, Philippe Lucien Bedard, Glenn J. Hanna · 发表于：Clinical Cancer Research · 年份：2025 · DOI：10.1158/1078-0432.ccr-25-0100 · 被引用次数：7 · 研究领域：Colorectal Cancer Treatments and Studies、TGF-β signaling in diseases、HER2/EGFR in Cancer Research

PURPOSE: To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of ficerafusp alfa (BCA101), a first-in-class bifunctional protein targeting EGFR and TGF-β, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors. PATIENTS AND METHODS: At escalating doses in a parallel 3 + 3 design, patients with EGFR-driven advanced solid tumors received weekly intravenous ficerafusp alfa as monotherapy (64-1,500 mg) or in combination (240-1,500 mg) with pembrolizumab (200 mg i.v. every 3 weeks). The primary objective was to determine safety/tolerability. Secondary objectives included assessment of pharmacokinetics, immunogenicity, and preliminary efficacy per investigator-assessed response. Exploratory analyses included pharmacodynamic biomarkers. RESULTS: Among 61 patients (monotherapy, n = 46; combination, n = 15), the most common treatment-related adverse events included acneiform dermatitis (46%) and fatigue (20%) with monotherapy and acneiform dermatitis (73%), fatigue (53%), pruritus (40%), epistaxis (40%), and maculopapular rash (40%) with combination therapy. One patient had a dose-limiting toxicity with 1,250-mg monotherapy (grade 3 anemia and hematuria). The MTD was not reached in either cohort. With monotherapy, objective response was observed in one of 42 evaluable patients and 16 (38%) achieved stable disease. With combination therapy, four of 13 evaluable patients (31%) had a confirmed response, including one with head and ...