A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC
Laurel B. Darragh, Michael W. Knitz, Junxiao Hu, Eric T. Clambey, Jennifer Backus, Andrew Dumit, Von Samedi, Andrew N. Bubak, Casey S. Greene, Timothy V. Waxweiler, Sanjana Mehrotra, Shilpa Bhatia, Jacob Gadwa, Thomas E. Bickett, Miles Piper, Kareem Fakhoury, Arthur Liu, Joshua H. Petit, Daniel W. Bowles, Ashesh A. Thaker, Kimberly Atiyeh, Julie Goddard, Robert Hoyer, Adrie van Bokhoven, Kimberly R. Jordan, Antonio Jimeno, Angelo D’Alessandro, David Raben, Jessica D. McDermott, Sana D. Karam
Abstract
Five-year survival for human papilloma virus-unrelated head and neck squamous cell carcinomas remain below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy with single-dose durvalumab (anti-PD-L1) neoadjuvantly (n = 21) ( NCT03635164 ). The primary endpoint of the study was safety, which was met. Secondary endpoints included radiographic, pathologic and objective response; locoregional control; progression-free survival; and overall survival. Among evaluable patients at an early median follow-up of 16 months (448 d or 64 weeks), overall survival was 80.1% with 95% confidence interval (95% CI) (62.0%, 100.0%), locoregional control and progression-free survival were 75.8% with 95% CI (57.5%, 99.8%), and major pathological response or complete response was 75% with 95% exact CI (51.6%, 100.0%). For patients treated with 24 Gy, 89% with 95% CI (57.1%, 100.0%) had MPR or CR. Using high-dimensional multi-omics and spatial data as well as biological correlatives, we show that responders had: (1) an increase in effector T cells; (2) a decrease in immunosuppressive cells; and (3) an increase in antigen presentation post-treatment.