Table 1.

Combination ICI Therapy Clinical Trials in HNSCC.

Target	Combination	Phase	Trial	Intent	Outcome
PD-1, CTLA-4	Nivolumab, Ipilimumab	3	NCT027441570 (CheckMate 651) [71]	Combination nivolumab + ipilimumab vs. EXTREME Regime (platinum/5-fluorouracil/cetuximab) for R/M HNSCC	Failed endpoint (OS). No difference between dual ICI blockade and EXTREME arm. Improvement in dual ICI arm if CPS > 20 (ns)
PD-L1, CTLA-4	Durvalumab, Tremelimumab	3	NCT02551159 (KESTRAL) [72]	Combination durvalumab + tremelimumab vs. duravalumab monotherapy vs. SOC CT in R/M HNSCC	Results pending
PD-1, CTLA-4	Nivolumab, Ipilimumab	2	NCT02823574 (CheckMate 714) [73]	Combination nivolumab + ipilimumab vs. nivolumab + ipilimumab placebo in R/M HNSCC	Failed ORR and OS endpoints. Subpopulation assessment ongoing.
PD-L1, CTLA-4	Durvalumab, Tremelimumab	3	NCT02369874 (EAGLE) [74,75]	Combination durvalumab + tremelimumab vs. durvalumab monotherapy vs. SOC in R/M HNSCC	Failed to meet primary OS improvement endpoint