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.

PURPOSE

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.

PATIENTS AND METHODS

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.

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 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.

CONCLUSION

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.