Table 1. Results of main clinical trials exploring immunotherapy in first-line treatment of NSCLC.

Study: characteristics	Treatment arms	N pts	OS		PFS		ORR (%)	AEs G3–5 (%)	IrAEs G3–5 (%)
Study: characteristics	Treatment arms	N pts	OS (months)	HR (95% CI); P value	PFS (months)	HR (95% CI); P value	ORR (%)	AEs G3–5 (%)	IrAEs G3–5 (%)
KN-001 (1): phase 1; NSCLC; PD-L1 ≥1%	Pembrolizumab	101	22.3	–	NA	–	41.6	13.0	4.0
KN-024 (3,4): phase 3; NSCLC; PD-L1 ≥50%	Pembrolizumab vs. platinum-based chemotherapy	154	26.3	0.65 (0.50–0.86); P=0.001	10.3	0.50 (0.37–0.68); P<0.001	44.8	31.0	13.0
KN-024 (3,4): phase 3; NSCLC; PD-L1 ≥50%	Pembrolizumab vs. platinum-based chemotherapy	151	14.2	0.65 (0.50–0.86); P=0.001	6.0	0.50 (0.37–0.68); P<0.001	27.8	53.0	1.0
KN-042 (5): phase 1; NSCLC; PD-L1 ≥1%	Pembrolizumab vs. platinum-based chemotherapy	637	16.7	0.81 (0.71–0.93); P=0.0018	5.4	1.07 (0.94–1.21)	27.3	17.8	8.0
KN-042 (5): phase 1; NSCLC; PD-L1 ≥1%	Pembrolizumab vs. platinum-based chemotherapy	637	12.1	0.81 (0.71–0.93); P=0.0018	6.5	1.07 (0.94–1.21)	26.5	41.0	1.5
KN-189 (6): phase 3; non-squamous NSCLC; any PD-L1 expression	Pembrolizumab + platinum-pemetrexed vs. placebo + platinum-pemetrexed	410	22.0	0.56 (0.45–0.70); P<0.00001	9.0	0.48 (0.40–0.58); P<0.00001	48.0	71.9	10.9
		206	10.7	0.56 (0.45–0.70); P<0.00001	4.9	0.48 (0.40–0.58); P<0.00001	19.4	66.8	4.5
KN-407 (7): phase 3; squamous NSCLC; any PD-L1 expression	Pembrolizumab + carboplatin-taxane vs. placebo + carboplatin-taxane	278	15.9	0.64 (0.49–0.85); P=0.0008	6.4	0.56 (0.45–0.70); P<0.0001	57.9	69.8	10.8
KN-407 (7): phase 3; squamous NSCLC; any PD-L1 expression		281	11.3	0.64 (0.49–0.85); P=0.0008	4.8	0.56 (0.45–0.70); P<0.0001	38.4	68.2	3.2
IMpower150 (8): phase 3; non-squamous NSCLC; any PD-L1 expression	Atezolizumab + arboplatin-paclitaxel and bevacizumab (Arm B) vs. carboplatin-paclitaxel and bevacizumab (Arm C)	400	19.2	0.78 (0.64–0.96); P=0.02	8.3	0.62 (0.52–0.74); P<0.001	63.5	67.5	NA
		400	14.7	0.78 (0.64–0.96); P=0.02	6.8	0.62 (0.52–0.74); P<0.001	48.0	63.7	NA
IMpower130 (9): phase 3; non-squamous NSCLC; any PD-L1 expression	Atezolizumab + carboplatin-nab-paclitaxel vs. carboplatin-nab-paclitaxel	451	18.6	0.79 (0.64–0.98); P=0.033	7.0	0.64 (0.54–0.77); P<0.0001	49.2	85.8	NA
		228	13.9	0.79 (0.64–0.98); P=0.033	5.5	0.64 (0.54–0.77); P<0.0001	31.9	76.3	NA
IMpower131 (10,11): phase 3; squamous NSCLC; any PD-L1 expression	Atezolizumab + carboplatin-nab-paclitaxel (Arm B) vs. carboplatin-nab-paclitaxel (Arm C)	343	14.2	0.88 (0.73–1.05); P=0.1581	6.3	0.71 (0.60–0.85); P=0.0001	49.0	82.0	13.0
		340	13.5	0.88 (0.73–1.05); P=0.1581	5.6	0.71 (0.60–0.85); P=0.0001	41.0	70.0	2.0
IMpower132 (12,13): phase 3; non-squamous NSCLC; any PD-L1 expression	Atezolizumab + platinum-pemetrexed vs. placebo + platinum-pemetrexed	292	18.1	0.81 (0.64–1.03); P=0.0797	7.6	0.60 (0.49–0.72); P<0.0001	47.0	69.0	NA
		286	13.6	0.81 (0.64–1.03); P=0.0797	5.2	0.60 (0.49–0.72); P<0.0001	32.0	59.0	NA
CheckMate 227 (14,15): phase 3; NSCLC; any PD-L1 expression	Nivolumab + ipilimumab vs. histology-based chemotherapy; TMB ≥10 mut/Mb	139	23.0	0.77 (0.56–1.06)	7.2	0.58 (0.41–0.81); P<0.001	45.3	32.8	NA
		160	16.7	0.77 (0.56–1.06)	5.5	0.58 (0.41–0.81); P<0.001	26.9	32.8	NA
	Nivolumab + ipilimumab vs. histology-based chemotherapy; PD-L1 ≥1%	396	17.1	0.79 (0.65–0.96); P=0.007	5.1	0.82 (0.69–0.97)	35.9	36.0	NA
		397	14.9	0.79 (0.65–0.96); P=0.007	5.6	0.82 (0.69–0.97)	30.0	36.0	NA

AEs of any cause are included in the table. KN-001: only data from treatment-naïve patients were reported (apart from toxicity); IMpower150: Arm B vs. Arm C data and results in the WT population are reported. IrAEs are only individually reported; IMpower130: IrAEs are only individually reported; IMpower131: Arm B vs. Arm C data are reported; IMpower132: IrAEs are only individually reported; CheckMate 227: the analysis of the dual primary endpoints are reported: PFS with nivolumab + ipilimumab vs. chemotherapy in patients with tumor mutational burden ≥10 mut/Mb (OS from Press Release) and OS for nivolumab + ipilimumab vs. chemotherapy in pts with tumor PD-L1 ≥1%). Treatment-related AEs are reported for all patients treated with nivolumab + ipilimumab or chemotherapy. IrAEs are only individually reported. OS, overall survival; PFS, progression free survival; ORR, overall response rate; AEs, adverse events; IrAEs, immune-related adverse events; N pts, number of patients; HR, hazard ratio; CI, confidence interval; KN, KEYNOTE; NSCLC, non-small cell lung cancer; PD-L1, programmed death ligand-1; NA, not available; WT, wild type.