. 2019 Nov;8(Suppl 3):S247–S264. doi: 10.21037/tlcr.2019.06.01

Table 1. Summary of reported pre-clinical half maximal inhibitory concentrations (IC₅₀) of third-generation EGFR TKIs for common EGFR mutations.

EGFR TKIs	Agents	Alterations in EGFR
EGFR TKIs	Agents	Ex19del^A,B	L858R^A,C	L858R/T790M^A,D	Ex19del/T790M^A,E	WT EGFR^A,F	Comments	Source
Osimertinib	AZD9291		12 nM*^‡	1 nM*^‡		184 nM*^‡		(33)
		56 nM^B1	36 nM^C	15 nM^D1	13 nM^E1	152 nM^F1		(35)
		41 nM^B1	26 nM^C	31 nM^D1	41 nM^E2			(36)
		7.9 nM^A	6.2 nM^A	0.9 nM^A	3.1 nM^A	516 nM^A		(37)
Nazartinib	EGF816	66 nM^A	35 nM^A	5.1 nM^A	52 nM^A	1,031 nM^A		(37)
Mavelertinib	PF-06747775	5 nM^B1	4 nM^C	12 nM^D1	3 nM^E1	307 nM^F1		(35)
Avitinib	AC0010			0.18 nM^‡		7.68 nM^‡	Kinase and cell-based assays are reported	(38)
Avitinib	AC0010	10.4 nM^B2		7.3 nM^D1 and 2.8 nM^D2		837 nM^F3	Kinase and cell-based assays are reported	(38)
Lazertinib	YH25448 GNS-1480	5.3 nM^‡	20.6 nM^‡	2.0 nM^‡	1.7 nM^‡	76.0 nM^‡	Kinase and cell-based assays are reported. See publication for cell-based assay results with other EGFR TKIs	(39)
Lazertinib	YH25448 GNS-1480	3.3 nM^A	3.9 nM^A	5.7 nM^A	4.9 nM^A	722.7 nM^A		(39)
Naquotinib	ASP8273	11 nM^B1	1.3 nM^C	6 nM^D1	5 nM^E2		Kinase and cell-based assays are reported. See publication for Ba/F3 cell-based assay results with other EGFR TKIs	(36)
Naquotinib	ASP8273	9 nM^A	11 nM^A	9 nM^A	10 nM^A	830 nM^A		(36)
Olmutinib	HM61713	9.2 nM^B2		10 nM^D1		2,225 nM^F2		(40)
Rociletinib	CO-1686	79 nM^B1	46 nM^C	16 nM^D1	9 nM^E1	1598 nM^F1		(35)
Erlotinib	–	11 nM^B1	10 nM^C	9,003 nM^D1	9,736 nM^E1	11 nM^F1		(35)
		15 nM^B1	10 nM^C	8,431 nM^D1	2,996 nM^E2			(36)
		73 nM^A	30 nM^A	>10,000 nM^A	3,429 nM^A	638 nM^A		(37)
		3.2 nM^B2		2,253 nM^D1		449 nM^F2		(40)
Gefitinib	–		<1 nM^‡	155 nM^‡		3 nM^‡		(33)
Afatinib	–		<1 nM*^‡	3 nM*^‡		3 nM*^‡		(33)
		2 nM^B1	0.08 nM^C	121 nM^D1	279 nM^E2			(36)
		0.6 nM^A	0.6 nM^A	179 nM^A	146 nM^A	30 nM^A		(37)
		1.8 nM^B2		53 nM^D1		31 nM^F2		(40)
Dacomitinib	–		<1 nM*^‡	10 nM*^‡		3 nM*^‡		(33)

*, reported apparent IC₅₀, due to time-dependent changes to enzyme activity with irreversible inhibitors; ^‡, assessed by kinase assay (see methods and supplemental methods from: (32,37,38); ^A, evaluated in Ba/F3 cells transduced with either mutated or wild-type EGFR, see (35,36,38); ^B, Exon 19 deletion evaluated in PC-9 cells (^B1) and HCC827 cells (^B2); ^C, L858R mutation evaluated in H3255 cells (^C); ^D, L858R/T790M mutation evaluated in H1975 cells (^D1) and NIH/3T3_TC32T8 cells (^D2); ^E, Ex19del/T790M evaluated in PC9-DRH cells (^E1) and PC9-ER cells (^E2); ^F, WT EGFR evaluated in A549 cells (^F1), H358 cells (^F2) and A431 (^F3). EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; WT, wild-type.

Table 1. Summary of reported pre-clinical half maximal inhibitory concentrations (IC50) of third-generation EGFR TKIs for common EGFR mutations.

Table 1. Summary of reported pre-clinical half maximal inhibitory concentrations (IC₅₀) of third-generation EGFR TKIs for common EGFR mutations.