Table 5.
Clinical trials of the combination of anti-PD-1/PD-L1 with chemotherapy in the first-line setting.
| Trial | PD-L1 assay | Phase | Histology | Design | PD-L1 status | ORR (%) | Median PFS (months) (HR, 95% CI) | Median OS (months) (HR, 95% CI) | ≥3 TRAE |
| Keynote-189 | Dako22C3 | III | nsq | Pembro + PEM + platin (410) PEM + platin (206) |
TPS ≥1% and <1% | 48.3% vs. 19.9% | 9.0 vs. 4.9 (HR 0.50; 0.41–0.59) |
22.0 vs. 10.6 (HR 0.60; 0.50–0.72) |
52.1% vs. 42.1% |
| TPS <1% (subgroup) | 33.1% vs. 14.3% | 6.2 vs. 5.1 (HR 0.68; 0.49–0.93) |
17.2 vs. 10.2 (HR 0.52; 0.37–0.72) |
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| TPS 1–49% (subgroup) | 50.0% vs. 20.7% | 9.4 vs. 4.9 (HR 0.54; 0.39–0.76) |
21.8 vs. 12.1 (HR 0.66; 0.47–0.93) |
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| TPS ≥50% (subgroup) | 62.1% vs. 25.7% | 11.1 vs. 4.8 (HR 0.50; 0.41–0.59) |
27.7 vs. 10.1 (HR 0.71; 0.50–1.00) |
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| Keynote-407 | Dako22C3 | III | sq | Pembro + TAX + CBP (278) TAX + CBP (281) |
TPS ≥1% and <1% | 62.6% vs. 38.8% | 8.0 vs. 5.1 (HR 0.59; 0.49–0.71) |
17.2 vs. 11.6 (HR 0.71; 0.59–0.86) |
74.8% vs. 70.0% |
| TPS <1% (subgroup) | 67.4% vs. 41.4% | 6.3 vs. 5.9 (HR 0.68; 0.50–0.93) |
15.0 vs. 11.0 (HR 0.78; 0.57–1.07) |
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| TPS ≥1% (subgroup) | 59.1% vs. 37.3% | 8.3 vs. 4.6 (HR 0.53; 0.42–0.67) |
18.7 vs. 12.8 (HR 0.68; 0.53–0.87) |
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| IMpower 130 | SP142 | III | nsq | Atezo + nP + CBP (483; WT 451) nP + CBP (240; WT 228) |
TC 0/1/2/3 IC 0/1/2/3 |
49.2% vs. 31.9% | 7.0 vs. 5.5 (HR 0.64; 0.54–0.77) |
18.6 vs. 13.9 (HR 0.79; 0.64–0.98) |
74.8% vs. 60.8% |
| TC3 or IC3 (subgroup) | – | 6.4 vs. 4.6 (HR 0.51; 0.34–0.77) |
17.3 vs. 16.9 (HR 0.84; 0.51–1.39) |
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| TC1/2 or IC1/2 (subgroup) | – | 8.3 vs. 6.0 (HR 0.61; 0.43–0.85) |
23.7 vs. 15.9 (HR 0.70; 0.45–1.08) |
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| TC0 and IC0 (subgroup) | – | 6.2 vs. 4.7 (HR 0.72; 0.56–0.91) |
15.2 vs. 12.0 (HR 0.81; 0.61–1.08) |
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| IMpower 132 | SP142 | III | nsq | Atezo + PEM + CBP (292) | TC 0/1/2/3 IC 0/1/2/3 |
47% vs. 32% | 7.6 vs. 5.2 (HR 0.60; 0.47–0.72) |
17.5 vs. 13.6 (HR 0.86; 0.71–1.06) |
58.4% vs. 43.1% |
| PEM + CBP (286) | TC3 or IC3 (subgroup) | 72% vs. 55% | 10.8 vs. 6.5 (HR 0.46; 0.22–0.96) |
NR vs. 26.9 (HR 0.73; 0.31–1.73) |
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| TC1/2 or IC1/2 (subgroup) | 38% vs. 38% | 6.2 vs. 6.7 (HR 0.80; 0.56–1.16) |
12.7 vs. 16.2 (HR 1.18; 0.80–1.76) |
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| TC0 and IC0 (subgroup) | 44% vs. 27% | 8.5 vs. 4.9 (HR 0.45; 0.31–0.64) |
15.9 vs. 10.5 (HR 0.67; 0.46–0.96) |
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| IMpower 131 | SP142 | III | sq | Atezo + nP + CBP (343) nP + CBP (340) |
TC 0/1/2/3 IC 0/1/2/3 |
49.7% vs. 41.0% | 6.3 vs. 5.6 (HR 0.71; 0.60–0.85) |
14.2 vs. 13.5 (HR 0.88; 0.73–1.05) |
69.2% vs. 58.4% |
| TC3 or IC3 (subgroup) | 61.7% vs. 31.8% | 10.1 vs. 5.1 (HR 0.41; 0.25–0.68) |
23.4 vs. 10.2 (HR 0.48; 0.29–0.81) |
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| TC1/2 or IC1/2 (subgroup) | 52.6% vs. 43.5% | 6.5 vs. 5.6 (HR 0.70; 0.54–0.91) |
12.8 vs. 15.5 (HR 1.08; 0.81–1.45) |
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| TC0 and IC0 (subgroup) | 43.8% vs. 41.5% | 5.7 vs. 5.6 (HR 0.82; 0.65–1.04) |
14.0 vs. 12.5 (HR 0.87; 0.67–1.03) |
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| CameL | Dako22C3 | III | nsq | Camre + PEM + CBP (205) PEM + CBP (207) |
TPS ≥1% and <1% | 60.5% vs. 38.6% | 11.3 vs. 8.3 (HR 0.60; 0.45–0.79) |
NR vs. 20.9 (HR 0.73; 0.53–1.02) |
69% vs. 47% |
| CameL-sq | Dako22C3 | III | sq | Camre + TAX + CBP (193) TAX + CBP (196) |
TPS ≥1% and <1% | 64.8% vs. 36.7% | 8.5 vs. 4.9 (HR 0.37; 0.29–0.47) |
NR vs. 14.5 (HR 0.55; 0.40–0.75) |
73.6% vs. 71.9% |
| RATIONALE 304 | SP263 | III | nsq | TIS + PEM + platin (223) PEM + platin (111) |
PD-L1 ≥1% and <1% | 57.4% vs. 36.9% | 9.7 vs. 7.6 (HR 0.65; 0.46–0.90) |
– | 67.6% vs. 53.6% |
| RATIONALE 307 | SP263 | III | sq | A: TIS + TAX + CBP (120) B: TIS + nP + CBP (118) C: nP + CBP (117) |
PD-L1 ≥1% and <1% | 73% vs. 75% vs. 50% | A vs. C: 7.6 vs. 5.5 (HR 0.52; 0.37–0.74) B vs. C: 7.6 vs. 5.5 (HR 0.48; 0.34–0.68) |
– | 85.8% vs. 83.9% vs. 80.3% |
| ORIENT-11 | Dako22C3 | III | nsq | Sinti + PEM + platin (266) PEM + platin (131) |
TPS ≥1% and <1% | 51.9% vs. 29.8% | 8.9 vs. 5.0 (HR 0.48; 0.36–0.64) |
NR vs. NR (HR 0.61; 0.40–0.93) |
61.7% vs. 58.8% |
| ORIENT-12 | Dako22C3 | III | sq | Sinti + GEM + platin (179) GEM + platin (178) |
TPS ≥1% and <1% | 44.7% vs. 35.4% | 5.5 vs. 4.9 (HR 0.54; 0.42–0.68) |
NR vs. NR (HR 0.57; 0.35–0.91) |
86.6% vs. 83.1% |
| CHOICE-01 | JS311 | III | nsq/sq | Tori + chemo (309) Chemo (156) |
TC ≥1% and <1% | 65.7% vs. 46.2% | 8.4 vs. 5.6 (HR 0.49; 0.39–0.61) |
NR vs. 17.1 (HR 0.69; 0.52–0.92) |
78.6% vs. 82.1% |
| GEMSTONE-302 | SP263 | III | nsq | Suge + PEM + CBP (191) PEM + CBP (96) |
PD-L1 ≥1% and <1% | 58.6% vs. 36.5% | 9.6 vs. 5.8 (HR 0.59; 0.45–0.79) |
22.8 vs. 17.7 (HR 0.67; 0.50–0.90) |
56.9% vs. 57.2% |
| sq | Suge + TAX + CBP (129) TAX + CBP (63) |
70.5% vs. 46.0% | 8.3 vs. 4.8 (HR 0.34; 0.24–0.48) |
Atezo: Atezolizumab; Camre: Camrelizumab; CBP: Carboplatin; CI: Confidence interval; EGFR: Epidermal growth factor receptor; GEM: Gemcitabine; HR: Hazard ratio; IC: Immune cells; nivo: Nivolumab; nP: Albumin-bound paclitaxel; NR: Not reached; NSCLC: Non-small cell lung cancer; nsq: Non-squamous NSCLC; ORR: Objective response rate; OS: Overall survival; PD1: Programed cell death protein 1; PD-L1: Programed cell death ligand 1; PEM: Pemetrexed; pembro: Pembrolizumab; PFS: Progression-free survival; platin: Platinum; Sinti: Sintilimab; sq: Squamous NSCLC; Suge: Sugemalimab; TAX: Paclitaxel; TC: Tumor cell; TIS: Tislelizumab; Tori: Toripalimab; TPS: Tumor proportion score; TRAE: Treatment related adverse events; WT: EGFR or ALK wild type. “–” represents unavailability of data. TC3 or IC3: PD-L1 expression on ≥50% of TC or on ≥10% of IC; TC2/3 or IC2/3: PD-L1 expression on ≥5% of TC or IC; TC1/2/3 or IC1/2/3: PD-L1 expression on ≥1% of TC or IC. TC0 and IC0: PD-L1 expression on <1% of TC and IC.