. 2018 Nov 5;30(1):44–56. doi: 10.1093/annonc/mdy495

Table 2.

Key trials defining a TMB threshold for ICB benefit

Cancer	Trial and treatment	Method	Threshold defined	RR	PFS	OS	Ref.
Melanoma	Anti-CTLA-4	WES	100 mutations			OS advantage	[39]
Melanoma	CM 038	WES	100 mutations			OS advantage in ipilimumab naive	[64]
Melanoma	Phase II nivolumab	WES	100 mutations			OS advantage in ipilimumab naive	[64]
NSCLC	KN 001 phase I/II	WES	200 mutations	59% versus 12%	NR versus 3.4 months		[40]
NSCLC	Pembrolizumab	WES	200 mutations	59% versus 12%	NR versus 3.4 months		[40]
NSCLC	BIRCH, FIR phase II	FM NGS	9.9 mut/Mb	25% versus 14%	HR 0.64	HR 0.87	[70]
NSCLC	Atezolizumab	FM NGS	9.9 mut/Mb	25% versus 14%	HR 0.64	HR 0.87	[70]
NSCLC	POPLAR randomized phase II atezolizumab versus docetaxel	FM NGS	9.9 mut/Mb	20% versus 4%	7.3 versus 2.8 months	16.2 versus 8.3 months	[70]
NSCLC	MSKCC: various immunotherapies	MSKCC NGS	7.4 mut/Mb	38.6% versus 25%			[68]
NSCLC	CM 012	WES	158 mutations	51% versus 13%	17.1 versus 3.7 months		[62]
NSCLC	Nivolumab/ipilimumab	WES	158 mutations	51% versus 13%	17.1 versus 3.7 months		[62]
NSCLC	CM 568	FM NGS	10 mut/Mb	44% versus 12%	7.1 versus 2.6 months		[71]
NSCLC	Nivolumab/ipilimumab	FM NGS	10 mut/Mb	44% versus 12%	7.1 versus 2.6 months		[71]
SCLC	CM 032 phase II nivolumab	WES	248 mutations	46.2% versus 21.3%	7.8 versus 1.4 months	22 versus 5.4 months	[63]
SCLC	versus nivolumab/ipilimumab	WES	248 mutations	46.2% versus 21.3%	7.8 versus 1.4 months	22 versus 5.4 months	[63]
NSCLC	CM 026 randomized phase III nivolumab versus chemotherapy	WES	>243 mutations	47% versus 23%	HR 0.62	HR 1.10	[42]
NSCLC	CM 227 randomized phase III nivolumab/ipilimumab versus chemotherapy	FM NGS	>10 mut/Mb	45.3% versus 24.6%	7.1 versus 3.2 months	NA	[77]
UC	CM 275 phase II	WES	≥170 versus <85 mutations	31.9% versus 10.9%	3 versus 2 months	11.63 versus 5.72 months	[78]
UC	Nivolumab	WES	≥170 versus <85 mutations	31.9% versus 10.9%	3 versus 2 months	11.63 versus 5.72 months	[78]
UC	IMvigor210 phase II	FM NGS	16 mut/Mb			OS advantage	[72]
UC	Atezolizumab	FM NGS	16 mut/Mb			OS advantage	[72]
UC	IMVigor211 phase III	FM NGS	>9.65 mut/Mb			HR 0.68	[73]
UC	Atezolizumab versus chemotherapy	FM NGS	>9.65 mut/Mb			HR 0.68	[73]
Solid tumor	Various immunotherapies	FM NGS	20 mut/Mb	58% versus 20%	12.8 versus 3.3 months	NR versus 16.3 months	[79]
Solid tumor	KN 028 and KN 012	WES	102 mutations	30% versus 7%	109 versus 59 days		[81]
Solid tumor	Pembrolizumab	WES	102 mutations	30% versus 7%	109 versus 59 days		[81]
HNSCC	KN 012 and KN 055 pembrolizumab	WES	175 mutations		HR 0.64	HR 0.98	[83]

CM, checkmate; KN, keynote; NSCLC, non-small-cell lung cancer; SCLC, small-cell lung cancer; UC, urothelial cancer; HNSCC, head and neck squamous cell carcinoma; WES, whole exome sequencing; NGS, next generation sequencing; HR, hazard ratio; NA, not applicable; mut, mutation; FM, Foundation Medicine.