Hernando-Calvo Alberto, Carvajal Richard D, Paik Paul K, Morris Van Karlyle, Zandberg Dan P, Kaczmar John M, Bohr David N, Reiners Ralf D, Gharakhani Elham, Salazar Rachel, Lizotte Patrick Hall, Ivanova Elena V, Bedard Philippe L, Hanna Glenn J
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Northwell Health, Lake Success, United States.
Clin Cancer Res. 2025 Jul 11. doi: 10.1158/1078-0432.CCR-25-0100.
To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of ficerafusp alfa (BCA101), a first-in-class bifunctional protein targeting epidermal growth factor receptor (EGFR) and TGF-β, as monotherapy and in combination with pembrolizumab, in patients with advanced solid tumors.
At escalating doses in a parallel 3+3 design, patients with EGFR-driven advanced solid tumors received weekly intravenous ficerafusp alfa monotherapy (64-1500 mg) or in combination (240-1500 mg) with pembrolizumab (200 mg intravenously 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 pharmacodynamics biomarkers.
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 1250-mg monotherapy (grade 3 anemia and hematuria). Maximum tolerated dose was not reached in either cohort. With monotherapy, objective response was observed in 1/42 evaluable patients; 16 (38%) achieved stable disease. With combination therapy, 4/13 evaluable patients (31%) had a confirmed response, including one with head and neck squamous cell carcinoma refractory to anti-programmed cell death 1 protein therapy and cetuximab. Prolonged neutralization of plasma TGF-β1 was observed at doses ≥500 mg.
Ficerafusp alfa exhibited a manageable safety profile and clinical activity as monotherapy and in combination with pembrolizumab, with exposure increasing proportionally at anticipated therapeutic doses.
