Immunotherapy combinations and chemotherapy sparing schemes in first line non-small cell lung cancer

Table 2 Summary of the main Phase III studies of IT combinations

Trial	Ph1	Drugs	Endpoints/outcome	PD-L1/TMB
				Population
				Subgroups
Checkmate 227	III	NI vs N vs CT1	OS PD-L1 > 1% and in non-selected population	PD-L1 ≥ 1%: NI 17 m vs CT 14.9 m, P = 0.007
			NI vs CT	PD-L1 < 1%: NI 17 m vs CT 12.2 m, P =0.007
			17 m vs 13.9 m
MYSTIC	III	DT vs D vs CT1	OS D vs CT OS and PFS DT vs CT PD-L1 > 25% population	PD-L1 > 25%: D vs CT1
				16 m vs 12 m, P = 0.04
				DT vs CT1 11.9 vs 12 m, P = 0.2
				TMB > 20
				DT vs CT1 21 m vs 10 m
Checkmate9LA	III	NI + CT1 X2 vs CT1 X4	OS in non selected population	NA
			OS NI-CT 15.6 m vs CT 10.9 m, P = 0.0006
CCTG BR.34	III	DT+ CT1 x 4 vs Durvalumab + tremelimumab (DT)	OS in non selected population	PD-L1 TPS ≥ 50%, DT-CT vs DT (HR 0.64, 95%CI: 0.40-1.04, P = 0.07). Plasma TMB < 20 mut/Mb was associated with shorter survival in both treatment groups (HR 1.99, 95%CI: 1.3-3.1)
			16.6 m DT-CT vs 14 m DT
CITYSCAPE	II	TA vs PA	ORR and PFS en PD-L1 > 1% PFS TA 7.7 m vs PA 3.2 m	PD-L1 > 50%
			ORR TA 37% vs PA 20%	PFS TA NA vs PA 4.1
				ORR TA 66 % vs PA 24%

¹Ph; Phase.

NI: Nivolumab + Ipilimumab; N: Nivo; DT: Tremelimumab + Durvalumab; D: Durvalumab; PD-1: Programed death-1; TMB: Tumor mutational burden; HR: Hazard ratio; CI: Confidence interval; TA: Tiragolumab + atezolizumab; PA: Placebo + atezolizumab; NA: Not available; CT: Chemotherapy.