Safety and Efficacy of Pembrolizumab in Combination with Acalabrutinib in Advanced Head and Neck Squamous Cell Carcinoma: Phase 2 Proof-of-Concept Study.
Clinical cancer research : an official journal of the American Association for Cancer Research
oregon; portland; chiles
PURPOSE: Programmed cell death-1 (PD-1) receptor inhibitors have shown efficacy in head and neck squamous cell carcinoma (HNSCC), but treatment failure or secondary resistance occurs in most patients. In preclinical murine carcinoma models, inhibition of Bruton's tyrosine kinase (BTK) induces myeloid cell reprogramming that subsequently bolsters CD8
EXPERIMENTAL DESIGN: Patients received pembrolizumab 200 mg intravenously every 3 weeks, alone or in combination with acalabrutinib 100 mg orally twice daily. Safety and overall response rate (ORR) were co-primary objectives. The secondary objectives were progression-free survival (PFS) and overall survival.
RESULTS: Seventy-six patients were evaluated (pembrolizumab,
CONCLUSIONS: Despite lack of clinical efficacy, immune subset analyses suggest that there are additive effects of this combination; however, the associated toxicity limits the feasibility of combination treatment with pembrolizumab and acalabrutinib in patients with recurrent or metastatic HNSCC.
Earle A. Chiles Research Institute
Taylor, Matthew H; Betts, Courtney B; Maloney, Lauren; Nadler, Eric; Algazi, Alain; Guarino, Michael J; Nemunaitis, John; Jimeno, Antonio; Patel, Priti; Munugalavadla, Veerendra; Tao, Lin; Adkins, Douglas; Goldschmidt, Jerome H; Cohen, Ezra E W; and Coussens, Lisa M, "Safety and Efficacy of Pembrolizumab in Combination with Acalabrutinib in Advanced Head and Neck Squamous Cell Carcinoma: Phase 2 Proof-of-Concept Study." (2021). Articles, Abstracts, and Reports. 5564.