2. Academic Validation
  3. 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

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

  • Clin Cancer Res. 2025 Nov 14;31(22):4623-4632. doi: 10.1158/1078-0432.CCR-25-0100.
Alberto Hernando-Calvo 1 2,  Richard D Carvajal 3,  Paul K Paik 4 5,  Van Karlyle Morris 6,  Dan P Zandberg 7,  John M Kaczmar 8,  David N Bohr 9,  Ralf D Reiners 10,  Elham Gharakhani 9,  Rachel L Salazar 11,  Patrick Hall Lizotte 12,  Elena V Ivanova 12,  Philippe L Bedard 1 2,  Glenn J Hanna 13
Affiliations

Affiliations

  • 1 Division of Hematology & Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
  • 2 Department of Medicine, University of Toronto, Toronto, Canada.
  • 3 Columbia University Irving Medical Center, New York, New York.
  • 4 Memorial Sloan Kettering Cancer Center, New York, New York.
  • 5 Weill Cornell Medical College, New York, New York.
  • 6 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • 7 UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.
  • 8 Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.
  • 9 Clinical Operations, Bicara Therapeutics, Boston, Massachusetts.
  • 10 Clinical Development, Bicara Therapeutics, Boston, Massachusetts.
  • 11 R&D Strategy and Operations, Bicara Therapeutics, Boston, Massachusetts.
  • 12 Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 13 Dana-Farber Cancer Institute, Boston, Massachusetts.
PMID: 40643947 DOI: 10.1158/1078-0432.CCR-25-0100
Abstract

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 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.

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