Table 3.

Association with TMB and benefit with ICIs in KEYNOTE-119 and IMpassion130

Trial	Agent(s) investigated	Number of patients evaluated for TMB (n TMB-H)	Outcomes: ORR; PFS HR (immunotherapy vs chemo); OS (immunotherapy vs chemo)
KEYNOTE-119	Pembrolizumab vs chemotherapy (investigator’s choice: capecitabine, eribulin, gemcitabine, or vinorelbine)	132 in pembrolizumab arm (n=12 TMB-H); 121 (n=14 TMB-H) in chemotherapy arm	TMB>10mut/Mb ORR 14.3% (95% CI 4% to 39.9%) vs 12.7% (95% CI 7.9% to 19.9%) PFS HR 1.14 (95% CI0.42 to 3.07) OS HR 0.58 (95% CI0.21 to 1.57)	TMB<10mut/Mb ORR 8.3% (95% CI 0.4% to 35.4%) vs 12.8% (95% CI 7.8% to 20.4%) PFS HR 1.24 (95% CI0.92 to 1.67) OS HR 0.81 (95% CI0.61 to 1.07)

Trial	Agents investigated	Biomarker evaluable population (median TMB 4.38 mut/Mb)	OS HR by TMB quartile, PD-L1 positive population (HR (95% CI))
			Quartile 1 (TMB 2.63 mut/Mb)	Quartile 2 (TMB 4.39 mut/Mb)	Quartile 3 (TMB 7.02 mut/Mb)
IMpassion130	Atezolizumab+chemotherapy vs placebo+chemotherapy	579 patients	0.69 (0.49 to 0.98)	0.59 (0.37 to 0.92)	0.37 (0.15 to 0.90)

chemo, chemotherapy; CI, confidence interval; HR, hazard ratio; mut/Mb, mutations per megabase; ORR, overall response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; TMB, tumor mutational burden; TMB-H, high TMB.