Phase 1-1b trial of neoadjuvant SBRT with single-dose durvalumab for HPV-unrelated locally advanced head and neck squamous cell carcinoma

Five-year survival of patients with HPV-unrelated locally advanced head and neck squamous cell carcinomas (LA HNSCC) is below 50%. A phase 1-1b trial at the University of Colorado Denver evaluated neoadjuvant hypofractionated SBRT in combination with single-dose durvalumab (anti-PD-L1) for these patients. The primary endpoint was safety, which was met. Among evaluable patients at an early median follow-up of 16 months, overall survival rate was 80.1% (95% CI 62.0-100.0), while locoregional control and progression-free survival rates were 75.8% (57.5-99,8) (no distant recurrences), and major pathologic response rate or complete response rate was 75% (51.6-100.0), while in the expansion cohort treated at the MTD (24 Gy) the response rate was 89% (57.1-100). Responders had an increase in effector T cells, a decrease in immunosuppressive cells, and an increase in antigen presentation post-treatment.