Table 3.

Selected multi-institutional, phase II/III clinical trials for pre-operative neoadjuvant radioimmunotherapy in HNSCC.

Trial	Est. No.	Arms	Primary Endpoint	Sequence	Est. Completion
KEYNOTE-689 [46]	704	CRT +/− neoadjuvant and adjuvant pembrolizumab	mPR, EFS	IO prior to and concurrent with RT: neoadjuvant pembrolizumab, then surgical resection, then CRT (cisplatin) with adjuvant pembrolizumab for high risk patients or RT with adjuvant pembrolizumab for low risk patients	7/2026
IMSTAR-HN [47]	276	CRT +/− neoadjuvant nivolumab with adjuvant IO (nivolumab +/− ipilimumab)	DFS	IO prior to and after RT: Neoadjuvant nivolumab, then surgical resection, then adjuvant RT or CRT (cisplatin), then maintenance nivolumamb +/− ipilimumab	5/2024
CompARE [48]	785	CRT +/− neck dissection as indicated vs. induction IO, then CRT +/− neck dissection as indicated, then IO	EFS, OS	IO prior to or after RT	12/2026

CRT—chemoradiotherapy, DFS—disease-free survival, EFS—event-free survival, HNSCC—head and neck squamous cell carcinoma, IO—immunotherapy, RT—radiotherapy, mPR—major pathological response.