Table 1

Summary of studies evaluating blood TMB as a predictive biomarker for response to immune checkpoint blockade

Study	Analysis	Approach	NGS assay	Panel size	Cohort size	Tumor type	Disease stage	Trial ID	Treatment	TMB cut-off
Khagi et al, 2017145	Retrospective	Targeted NGS	Guardant 360 (73 genes)	200 Kb	n=69	Pan-cancer	Not reported	N/A	Anti-PD1/PDL1/CTLA4	VUS, >3 alterations
Gandara et al, 201860	Retrospective	Targeted NGS	Custom NGS assay (bait set version T7, Integrated DNA Technology, >300 genes)	1.1 Mb	n=259	NSCLC	Advanced/metastatic	POPLAR (NCT01903993); OAK (NCT02008227)	Atezolizumab vs docetaxel	16 Mutations/Mb
Wang et al, 2019146	Retrospective	Targeted NGS	Custom assay (NCC-GP150, 150 genes)	Not reported	n=48 cohort 1; n=50 cohort 2	NSCLC	Advanced/metastatic	N/A	Anti-PD-1/PD-L1	6 Mutations/Mb
Si et al, 202163	Retrospective	Targeted NGS	Guardant OMNI (500 genes)	2 Mb	n=1001	NSCLC	Metastatic	MYSTIC (NCT02453282)	Durvalumab and tremelimumab vs chemotherapy	20 Mutations/Mb
de Castro Jr et al, 202265	Prospective	Targeted NGS	Guardant OMNI (500 genes)	2 Mb	n=512	NSCLC	Metastatic	NEPTUNE (NCT02542293)	Durvalumab and tremelimumab versus chemotherapy	20 Mutations/Mb
Kim et al, 202266	Prospective	Targeted NGS	Foundation Medicine (>300 genes)	1.1 Mb	n=152	NSCLC	Locally advanced/metastatic	B-F1RST (NCT02848651)	Atezolizumab	16 Mutations/Mb
Peters et al, 202268	Prospective	Targeted NGS	Foundation Medicine (>300 genes)	1.1 Mb	n=472	NSCLC	Advanced/metastatic	BFAST (NCT03178552)	Atezolizumab versus chemotherapy	16 Mutations/Mb
He et al, 202269; Schenker et al, 202270	Prospective	Targeted NGS	Foundation Medicine (>300 genes)	1.1 Mb	n=212	Pan-cancer	Advanced/metastatic	CheckMate 848 (NCT03668119)	Nivolumab+ipilimumab vs nivolumab monotherapy	10 Mutations/Mb

BFAST, Blood First Assay Screening Trial; bTMB, blood tumor mutation burden; N/A, not available; NGS, next-generation sequencing; NSCLC, Non-small cell lung cancer; VUS, variants of unknown significance.