Data from 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
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AbstractPurpose: 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 neck squamous cell carcinoma refractory to anti–PD-1 therapy and cetuximab. Prolonged neutralization of plasma TGF-β1 was observed at doses ≥500 mg. Conclusions: 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. See related commentary by Choudhury et al., p. 4617