表4.

正在研发或已获批EGFR外显子20插入突变靶向药物临床研究汇总

Type	Stage	Drug name	Trial registration number	Phase	Regimen	Enrolled population	Primary efficacy endpoint and outcome	Additional important efficacy outcome	Ref.
EGFR Ex20ins target	Approved indication study/Phase III clinical drug	TAK-788, Mobocertinib	NCT02716116	II	Mobocertinib 160 mg qd until progressive disease	Advanced NSCLC patients with EGFR ex20ins, who received platinum-based chemotherapy	cORR (IRC): 28%	cORR (INV): 35%; DCR (IRC): 78%; DOR (IRC): 15.8 mon; PFS (IRC): 7.3 mon; OS: 20.2 mon	[51]
			NCT04129502	III	Mobocertinib (160 mg qd) vs Platinum-based chemotherapy	Advanced NSCLC with EGFR ex20ins, first-line treatment	PFS (IRC) (Unpublished)	-	[53]
		Amivantamab	NCT02609776	I	Amivantamab 1,050 mg (baseline weight <80 kg) or 1,400 mg (baseline weight≥80 kg)	Advanced NSCLC patients with EGFR ex20ins, who received platinum-based chemotherapy	cORR (IRC): 39.5%	cORR (INV): 35.8% DOR (IRC): 11.1 mon; PFS (IRC): 8.3 mon; OS: 22.8 mon	[55]
			NCT04538664	III	Amivantamab+ platinum-based chemotherapy vs Platinum-based chemotherapy	Advanced NSCLC with EGFR ex20ins, first-line treatment	PFS (IRC) (Unpublished)	-	[56]
	Phase I/II clinical drug	Poziotinib	NCT03318939	II	Poziotinib 16 mg qd until progressive disease	Advanced NSCLC patients with EGFR ex20ins, who received platinum-based chemotherapy (cohort 1)	ORR: 14.8%	DCR: 68.7%; DOR: 7.4 mon; PFS: 4.2 mon	[58]
						Advanced NSCLC with EGFR ex20ins, first-line treatment (cohort 3)	cORR: 27.8%	DCR: 86.1%; DOR: 6.5 mon; PFS: 7.2 mon	[59]
		Sunvozertinib (DZD9008)	CTR20211009	II	Sunvozertinib 300 mg qd	Advanced NSCLC patients with EGFR ex20ins, who received platinum-based chemotherapy	ORR (BICR): 59.8%	-	[60]
		TAS6417 (CLN-081)	NCT04036682	I/II	TAS6417	Advanced NSCLC patients with EGFR ex20ins, who received platinum-based chemotherapy	cPR rate: 38.4%	DOR: 10 mon; PFS: 10 mon	[62]
		AP-L1898	NCT04993391	I/II	AP-L1898	Advanced NSCLC with EGFR ex20ins	ORR (Unpublished)	-	[64]
		HS-10376	NCT05435274	I/II	HS-10376	Previously treated, advanced NSCLC with EGFR ex20ins	ORR (Unpublished)	-	[64]
		BLU-451	NCT05241873	I/II	BLU-451	Advanced NSCLC with EGFR ex20ins	ORR (Unpublished)	-	[64]
		JS 111	NCT04993391	I/II	JS 111	Previously treated, advanced NSCLC with EGFR ex20ins	ORR (Unpublished)	-	[64]
		FWD1509	NCT05068024	I/II	FWD1509	Previously treated, advanced NSCLC with HER2/EGFR ex20ins	ORR (Unpublished)	-	[64]
		BAY 2927088	NCT05099172	I	BAY 2927088	Previously treated, advanced NSCLC with HER2/EGFR ex20ins	ORR (Unpublished)	-	[64]
		PLB1004	NCT05347628	I	PLB1004	Advanced NSCLC with HER2/EGFR ex20ins	ORR (Unpublished)	-	[64]
		YK-029A	CTR20180350	I	YK-029A	Advanced NSCLC with HER2/EGFR ex20ins	ORR (Unpublished)	-	[37]
Type	Stage	Drug name	Trial registration number	Phase	Regimen	Enrolled population	Primary efficacy endpoint and outcome	Additional important efficacy outcome	Ref
Traditional EGFR-TKIs	-	Osimertinib	NCT03191149	II	Osimertinib 160 mg qd	Previously treated, advanced NSCLC with EGFR ex20ins	cORR: 25%	PFS: 9.7 mon	[47]
			NL6705	II		Advanced NSCLC with EGFR ex20ins, first-line treatment	ORR: 28%	PFS: 6.8 mon OS: 15.2 mon	[48]
		Furmonertinib	NCT04858958	I	Furmonertinib 240 mg qd	Advanced NSCLC with EGFR ex20ins, first-line treatment	ORR: 70%	-	[49]
		Afatinib	NCT03727724	II	Afatinib 40 mg QD, cetuximab 500 mg/m² q2w	Advanced NSCLC with EGFR ex20ins	18-week DCR rate: 59%	ORR: 47% PFS: 5.5 mon	[50]
Other therapies	-	NVP-AUY922	NCT01854034	II	AUY922 70 mg/m2 qw	Previously treated, advanced NSCLC with EGFR ex20ins	ORR: 17%	-	[63]
		Tarloxotinib	NCT03805841	II	Tarloxotinib	Previously treated, advanced NSCLC with EGFR ex20ins	ORR (Unpublished)	-	[64]

ORR: objective response rate; IRC: Independent Review Committee; INV: Investigator; cORR: confirmed objective response rate; BICR: blinded independent central review; cPR: confirmed partial response; DCR: disease control rate; qd: once a day; q2w: once every two weeks; EGFR: epidermal growth factor receptor; TKIs: tyrosine kinase inhibitors; PFS: progression-free survival; OS: overall survival; DOR: duration of response.