Immune checkpoint inhibitors in head and neck squamous cell carcinoma: A systematic review of phase-3 clinical trials

Table 2 Major ongoing phase-3 studies investigating immunotherapy in head and neck squamous cell carcinoma

Study	Status/trial ID	Population	Intervention	Control	No of participants	Target receptor
KESTREL[47]	Active, not recruiting/NCT02551159	R/M HNSCC	Arm 1: Durvalumab	EXTREMEregime	823	PDL-1, CTLA-4
			Arm 2: Durvalumab with Tremelimumab
Checkmate 651[48]	Active, not recruiting/NCT02741570	R/M HNSCC	Nivolumab with Ipilimumab	EXTREME regime	947	PD-1, CTLA-4
LEAP-10[49]	Active, recruiting/NCT04199104	R/M HNSCC	Pembrolizumab with Lenvatinib	Pembrolizumabwith placebo	500	PD-1, VEGF-multiple kinase
ECHO-304/KEYNOTE 669[50]	Active, not recruiting/NCT03358472	R/M HNSCC	Arm1: Pembrolizumab with Epacadostat	EXTREME	625	PD-1,IDO1
			Arm 2: Pembrolizumab alone
KEYNOTE 412[51]	Active, not recruiting/NCT03040999	LAHNSCC	Pembrolizumab with CRT concurrently and as maintenance	Standard CRT plus placebo	780	PD-1
REACH[52]	Active, not recruiting/NCT02999087	LAHNSCC	Avelumab in combination with RT-cetuximab	Cisplatin-RT and/or RT-cetuximab alone	707	PD-L1
HN004[53]	Active, recruiting/NCT03258554	LAHNSCC	Durvalumab plus RT	Cetuximab plus RT	474	PD-L1
		Platinum in eligible patients
CheckMate 9TM[54]	Completed awaiting results/NCT03349710	LAHNSCC	Nivolumab plus RT	Cetuximab plus RT	68	PD-1
		Platinum ineligible cohort
		LAHNSCC	Nivolumab pluscisplatin plus RT	Cisplatin plus RT
		Platinum eligible cohort
KEYNOTE 689[55]	Active, recruiting/NCT03765918	LAHNSCC	Pembrolizumab with RT (with or without cisplatin) before and after surgery	RT (with or without cisplatin) given after surgery	704	PD-1
iMvoke010[56]	Active, recruiting/NCT03452137	LAHNSCC	Atezolizumab as adjuvant therapy after definitive local therapy	Placebo	400	PD-L1
IMSTAR-HN[57]	Active, not recruiting/NCT03700905	Surgically resectable LAHNSCC	Nivolumab alone or in combination Ipilimumab as follow up after adjuvant therapy	Standard follow-up after adjuvant therapy	276	PD-1, CTLA-4
NIVOPOSTOP[58]	Active, recruiting/NCT03576417	LAHNSCC	Adjuvant Nivolumab with CRT postoperatively	CRT alone post operatively	680	PD-1

CRT: Chemoradiation therapy; R/M HNSCC: Recurrent or metastatic head and neck squamous cell carcinoma; LAHNSCC: Locally advanced head and neck squamous cell carcinoma; PD-1: Programmed cell death protein-1; PD-L1: Programmed death-ligand 1; CTLA-4: Cytotoxic T- lymphocyte associated protein-4; IDO1: Indoleamine 2,3-dioxygenase 1; VEGF: Vascular endothelial growth factor.