922P Dose Expansion Results of the Bifunctional EGFR/TGFβ Inhibitor BCA101 with Pembrolizumab in Patients with Recurrent, Metastatic Head and Neck Squamous Cell Carcinoma

Pembrolizumab (P) is approved for recurrent, metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). BCA101 is a first-in-class bifunctional EGFR/TGFβ inhibitor with a manageable safety profile and preliminary efficacy in advanced solid tumors ( ESMO 2022 731MO). Here we report the preliminary results from the fully enrolled expansion cohort combining BCA101+P as first line therapy in R/M HNSCC. This ongoing single-arm, multicenter dose expansion cohort enrolled patients (pts) with R/M HNSCC, PD-L1 CPS≥1 with no prior systemic therapy for R/M disease, ECOG 0-1, and measurable disease (RECIST v1.1). Pts received BCA101 (1500 mg IV on days 1, 8, 15) with P (200 mg IV on day 1) every 21-days. Primary endpoint: safety; secondary endpoints: overall response rate (ORR), duration of response, progression-free survival (PFS), overall survival. Exploratory: molecular and immunologic predictors of response. Thirty-one of 33 pts were evaluable and each had at least two restaging scans. Pts were more often men (n=23, 70%); median age: 65 (range: 31-80). Eighteen (55%) had baseline PD-L1 CPS scores of 1-19, 15 (45%) were ≥20. Oropharynx (19, 58%) [12/19 (63%) HPV/p16+] and oral cavity (10, 30%) were the most common subsites. Twenty-five pts (76%) had distant disease. The ORR was 48% (1 CR, 14 PRs) with 65% (13/20) of HPV(-) pts achieving a response, including 5/10 (50%) responders with CPS 1-19. Median PFS has not been reached among HPV(-) pts with 13/20 responses ongoing (five >6 months). Grade 3+ treatment-related adverse events (TRAEs) were observed in 9/33 pts (27%). There were no treatment-related deaths. Acneiform rash was the most common TRAE of any grade (24/33, 73%). Response data for the full cohort (n=39) will be available at the time of the meeting. BCA101+P exhibits encouraging anti-tumor activity particularly among HPV(-) pts, and the combination is well tolerated among this R/M HNSCC population. Further investigation is warranted.