Abstract CT034: Dose expansion results of single agent ficerafusp alfa (BCA101), a bifunctional EGFR/TGFβ inhibitor in patients with metastatic or advanced cutaneous squamous cell carcinoma (CSCC)

Abstract Purpose/Objective(s): Ficerafusp alfa (BCA101) is a first-in-class bifunctional EGFR/TGFβ inhibitor with a manageable safety profile and preliminary efficacy in advanced solid tumors (ASCO 2023). Here we report the preliminary safety and efficacy of ficerafusp alfa monotherapy in patients with metastatic or advanced CSCC, after failure of anti-PD-1 treatment. Introduction: CSCC is one of the most common cancers, For patients with advanced CSCC (unresectable and/or distant metastases) anti-PD1 therapy is the standard of care achieving durable responses in < 50% of the patients. However, for patients who progress on or are refractory to anti-PD1, there is no approved second-line therapy. Materials/Methods: This ongoing single-arm, multicenter dose expansion cohort enrolled patients (pts) with CSCC as part of a phase 1/1b trial. Eligible patients must have received prior anti-PD-1 therapy for advanced disease and must not have received anti-EGFR antibodies in the unresectable/metastatic setting. Pts received ficerafusp alfa 1500 mg IV weekly until disease progression, intolerance, or withdrawal. Primary endpoint: safety and tolerability; secondary endpoints: overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival. Exploratory endpoints: molecular and immunologic predictors of response. Results: As of July 15, 2024, 14 patients had received at least one dose of study drug, and 12 pts were efficacy evaluable. Most patients were men (12, 86%) and white (13, 93%); the median age was 73 (range: 36-92 years), none received concomitant radiation during treatment. Most (67%) of the evaluable population had PD as best response to prior anti-PD-1 therapy. Among the evaluable population, the ORR per RECIST 1.1 was 42% (95%CI 15.2-72.3%) with 5 PR (no CRs), 6 with SD, yielding a DCR of 92%; Median PFS was 5.5 months (range,3.1 - NR). Nine patients discontinued treatment, including 5 due to disease progression. At the time of the cut-off 5 patients remained ongoing. TRAEs were observed in 13/14 (93%) of patients, most common TRAEs of any grade were acneiform dermatitis (64%), pruritus, dry skin and fatigue (21% each). Grade 3 TRAEs were observed in 5 (36%), most common Grade 3TRAE was anemia in 2 (14%) patients. There were no TRAEs leading to death or permanent discontinuation of study treatment. Conclusion: Ficerafusp alfa was well tolerated and demonstrated encouraging single agent activity in CSCC patients previously treated with anti-PD1. Further investigation of ficerafusp alfa in pts with metastatic or advanced CSCC alone and in combination with immunotherapy is warranted. Updated data will be presented. Citation Format: John M. Kaczmar, Eric Sherman, Gino K. In, Glenn J. Hanna, Christine H. Chung, Tamara A. Sussman, Neal S. Akhave, Fiona Day, Danny Rischin, Allen Lau, Rachel L. Salazar, Deborah J. Wong. Dose expansion results of single agent ficerafusp alfa (BCA101), a bifunctional EGFR/TGFβ inhibitor in patients with metastatic or advanced cutaneous squamous cell carcinoma (CSCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT034.