Perioperative immunotherapy for esophageal squamous cell carcinoma: Now and future

Table 2 Ongoing clinical trials of neoadjuvant immunotherapy for resectable esophageal squamous cell carcinoma

Drug & target	Trial name/No./Ref.	Phase	Sample size	Clinical stage	Design	Chemotherapy drugs	Chemotherapy cycles	Radiotherapy	Interval to surgery	Primary endpoint	Start date
Nivolumab	FRONTiER/NCT03914443[67]	I	36	IC-IVA	Two-arm	5-FU + DDP	2, Q3W		12 wk	Incidence of dose-limiting toxicities	07-May-19
	NCT03987815	II	20	NA	Single-arm	NA				MPR	01-Aug-19
	NCT05213312	II-III	90	II-III	Two-arm	PTX/5-FU + DDP	2, Q3W		4-6 wk	pCR	01-Jun-22
Pembrolizumab	PALACE-1/NCT03792347[85]	I	20	IC-IVA	Single-arm	CBP + PTX	5, Q1W	41.4 Gy/23 f	4-6 wk	Safety	21-Jan-19
	PALACE-2/NCT04435197[84]	II	143	IC-IVA	Single-arm	CBP + PTX	5, Q1 W	41.4 Gy/23 f	4-6 wk	pCR	11-Aug-20
	NCT05302011	II	30	IIB/IIIB/IVA	Single-arm	CBP/DDP + DTX	4, Q3W			Tumor response, pCR	01-Jun-20
	NCT05281003	II	128	IC-IVA	Single-arm	PTX + DDP	4, Q4W			pCR	20-Feb-23
Camrelizumab	NCT04520035	II	60	IIB-IVA	Single-arm	PTX + DDP	2, Q3W			pCR	01-Aug-20
	NCT04767295	II	28	IA-IVA	Single-arm	nab-PTX + CBP	2, Q3W		5-8 wk	pCR	01-Mar-21
	NICE-2 Study/NCT 05043688[128]	II	204	Locally advanced	Three-arm	nab-PTX, CBP, PTX	2, Q3W	41.4 Gy/23 f	4-12 wk	pCR	14-Sep-21
	NCT05476380	II	39	IIIB-IVA	Single-arm	PTX + DDP	3, Q3W			pCR	19-Feb-21
	NCT05182944	II	130	IIB-IVA	Four-arm	nab-PTX + DDP	2, Q3W			pCR, 3-yr DFS	15-Jan-22
	NCT04937673	II	40	IIB-IVA	Two-arm	PTX/nab-PTX + DDP	3, Q3W		NA	Biomarkers related to pCR	01-Jul-21
	NCT05176002	I-II	26	II-IVA	Single-arm	NA	NA	Radiotherapy, NA	NA	Efficacy Safety	23-Sep-21
	NCT04666090	II	42	IIA-IVA	Single-arm	nab-PTX + NDP + Apatinib	2-3, Q2W		4-6wk	pCR	23-Nov-20
	NCT05355168	I-II	57	IC-IVA	Single-arm	Nimotuzumab + CRT	NA			pCR, MPR	01-Nov-21
	NCT03200691	II	21	IIA-III	Single-arm			40 Gy/20 f	2-4 wk	pCR	10-Aug-17
Sintilimab	NCT03940001	I	20	IIB-IVA	Single-arm	PTX + CBP	2, Q3W	41.4 Gy/23 f	NA	Unacceptable toxicity; pCR; MPR	01-May-19
	(NICCE)NCT05028231	NA	46	IIB-IVA	Single-arm	nab-PTX + DDP	2, Q3W			pCR	05-Jun-21
	NCT05357846	III	422	IIB-IVA	Two-arm	PTX + DDP	4, Q1W	40 or 45 Gy / 20 f	6-8 wk	OS	01-Nov-22
	NCT05244798	III	420	IC-IVA	Three-arm	nab-PTX + CBP	2, Q3	41.4 Gy/23 f	6-8 wk	pCR	01-Nov-22
Toripalimab	NCT04280822	III	400	IC-IVA	Two-arm	DDP + PTX	2, Q3W		2-3 wk	3 yr EFS; 5 yr EFS	21-Apr-20
	NCT04804696	II	53	NA	Single-arm	PTX + DDP	NA		NA	pCR	10-Feb-21
	NCT04177875	II	44	IC-IIIB	Single-arm	DTX/PTX + DDP	2, Q3W	40 Gy/20 f	NA	MPR; ORR	01-May-19
	NCT04888403	II	45	IIB-IVA	Single-arm	nab-PTX + NDP	5, Q1W	41.4 Gy/23 f	Within 7 wk	pCR	31-Dec-21
	NCT04644250	II	32	IIB-IVA	Single-arm	CBP + PTX liposome	5, Q1W	41.4 Gy/23 f	2-4 wk	pCR	01-Sep-20
	NCT04848753	III	632	IC-IVA	Two-arm	DDP + PTX	NA		NA	EFS	18-Jun-21
	NCT04006041	II	44	IIB-IVA	Single-arm	PTX + DDP	4, Q1W	44 Gy/20 f	6-8 wk	pCR	25-Jun-19
Tislelizumab	iCROSS/NCT04973306	II-III	176	II-III	Two-arm	CBP + PTX	5, Q1W	41.4 Gy/23 f	NA	pCR; OS	02-Mar-22
	NCT05323890	II	15	IIB-IVA	Single-arm	nab-PTX + DDP	5, Q1W	41.4 Gy/23 f	NA	MPR, pCR	20-Apr-22
	NCT04974047	II	70	IIB-IVA	Two-arm	PTX/5-FU + DDP	2, NA	40 or 45 Gy/20 fractions	NA	pCR	17-Aug-21
	NCT05189730	II	80	II-III	Single-arm	PTX + CBP	2, Q3W	40 Gy/20 f	4-6 wk	pCR, incidence of adverse events	01-Jul-21
Adebrelimab (PD-L1)	NATION1907II/NCT04215471	II	30	Resectable	Single-arm					ORR	01-Feb-20
Durvalumab	NCT04568200	II	60	IIB-IVA	Two-arm	CBP + PTX	4, Q3W	41.4 Gy/23 f		pCR	19-Jun-20
Pembrolizumab (+ Adjuvant)	KEYSTONE-002/NCT04807673[86]	III	342	IC-IIIB	Two-arm	PTX + DDP	3, Q3W	41.4 Gy/23 f	4-6 wk	EFS	01-Dec-21
PD-1 Inhibitor	REVO/NCT05007145	II	92	IB-IVA	Two-arm	nab-PTX + DDP	2-4, Q3W	40 Gy/20 f		pCR	15-Aug-21
Toripalimab (+ Adjuvant)	NCT 04437212	II	20	IIB-IVA	Single-arm	PTX/DDP	5, Q3W	41.4 Gy/23 f	6-8 wk	MPR	01-Jul-20

EFS: Events-free survival; DFS: Disease-free survival; OS: Overall survival; ORR: Objective response rate; NA: Not available; 5-FU: 5-fluorouracil; DDP: Cisplatin; PTX: Paclitaxel; DTX: Docetaxel; CBP: Carboplatin; NDP: Nedaplatin; nab-PTX: Paclitaxel for injection (albumin bound); pCR: Pathological complete response; MPR: Major pathological response.