Table 3 Frontline immunotherapies for advanced-stage NSCLC
From: Advances in molecular pathology and therapy of non-small cell lung cancer
Therapeutic settings | Trial names | Assessed regimes | Trial interventions | PD-L1 status | Primary endpoints | Regulatory status |
|---|---|---|---|---|---|---|
Single-agent immunotherapy | KEYNOTE-024 Phase III (NCT02142738)335 | Pembrolizumab | Pembrolizumab vs. Chemotherapy | PD-L1 TPS ≥ 50% | PFS: 10.3 months vs. 6.0 months | FDA-approved/2016 |
|  | IMPOWER110 Phase III (NCT02409342)336 | Atezolizumab | Atezolizumab vs. Chemotherapy | PD-L1 TPS or IC ≥ 1% | OS: 17.5 months vs. 14.1 months (PD-L1 ≥ 1%); 20.2 months vs. 13.1 months (PD-L1 ≥ 50%) | FDA-approved/2020 (only PD-L1 ≥ 50%) |
|  | EMPOWER-Lung 1 Phase III (NCT03088540)437 | Cemiplimab | Cemiplimab vs. Chemotherapy | PD-L1 TPS ≥ 50% | OS: 26.1 months vs. 13.3 months PFS: 8.1 months vs. 5.3 months | FDA-approved/2021 |
|  | KEYNOTE-042 Phase III (NCT02220894)339 | Pembrolizumab | Pembrolizumab vs. Chemotherapy | PD-L1 TPS ≥ 1% | OS: 16.7 months vs. 12.1 months | FDA-approved/2019 |
Immunotherapy in combination with chemotherapy | KEYNOTE-021 Phase II (NCT02039674)846 | Pembrolizumab + Chemotherapy (Non-squamous) | Pembrolizumab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | ORR: 55% vs. 29% PFS: 13.0 months vs. 8.9 months | FDA-accelerated approval/2017 |
| Â | KEYNOTE-189 Phase III | Pembrolizumab + Chemotherapy (Non-squamous) | Pembrolizumab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | OS: 22.0 months vs. 10.7 months PFS: 9.0 months vs. 4.9 months | FDA- traditional approval /2018 |
| Â | KEYNOTE-407 Phase III (NCT02775435)849 | Pembrolizumab + Chemotherapy (Squamous) | Pembrolizumab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | OS: 15.9 months vs. 11.3 months PFS: 6.4 months vs. 4.8 months | FDA-approved/2018 |
| Â | IMPOWER130 Phase III (NCT02367781)343 | Atezolizumab + Chemotherapy (Non-squamous) | Atezolizumab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | OS: 18.6 months vs. 13.9 months PFS: 7.0 months vs. 5.5 months | FDA-approved/2019 |
| Â | IMPOWER131 Phase III (NCT02367794)850 | Atezolizumab + Chemotherapy (Squamous) | Atezolizumab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | OS: 14.2 months vs. 13.5 months PFS: 6.3 months vs. 5.6 months | Â |
| Â | EMPOWER-Lung 3 Phase III (NCT03409614)851 | Cemiplimab + Chemotherapy | Cemiplimab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | OS: 21.9 months vs. 13.0 months PFS: 8.2 months vs. 5.0 months | FDA-approved/2022 |
| Â | ORIENT-11 Phase III (NCT03607539)852 | Sintilimab + Chemotherapy (Non-squamous) | Sintilimab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 8.9 months vs. 5.0 months | NMPA-approved/2021 |
| Â | ORIENT-12 Phase III (NCT03629925)853 | Sintilimab + Chemotherapy (Squamous) | Sintilimab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 5.1 months vs. 4.9 months | NMPA-approved/2021 |
| Â | CAMEL Phase III (NCT03134872)854 | Camrelizuab + Chemotherapy (Non-squamous) | Camrelizuab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 11.3 months vs. 8.3 months | NMPA-approved/2020 |
| Â | CAMEL-sq Phase III (NCT03668496)855 | Camrelizuab + Chemotherapy (Squamous) | Camrelizuab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 8.5 months vs. 4.9 months | NMPA-approved/2021 |
| Â | CHOICE-01 Phase III (NCT03856411)352 | Toripalimab + Chemotherapy | Toripalimab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 8.4 months vs. 5.6 months | NMPA-approved/2022 |
| Â | RATIONALE 304 Phase III (NCT03663205)856 | Tislelizumab + Chemotherapy (Non-squamous) | Tislelizumab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 9.7 months vs. 7.6 months | NMPA-approved/2021 |
| Â | RATIONALE 307 Phase III (NCT03594747)348 | Tislelizumab + Chemotherapy (Squamous) | Tislelizumab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 7.6 months vs. 5.5 months | NMPA-approved/2021 |
| Â | ASTRUM-004 Phase III (NCT04033354)351 | Serplulimab + Chemotherapy (Squamous) | Serplulimab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 8.3 months vs. 5.7 months | NMPA-approved/2022 |
| Â | AK105-302 Phase III (NCT03866993)353 | Penpulimab + Chemotherapy (Squamous) | Penpulimab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 7.6 months vs. 4.2 months | NMPA-approved/2023 |
| Â | GEMSTONE-302 Phase III | Sugemalimab + Chemotherapy | Sugemalimab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 7.8 months vs. 4.9 months OS: 25.4 months vs. 16.9 months | NMPA-approved/2021 |
Immunotherapy with dual ICIs | CHECKMATE-227 Phase III (NCT02477826)859 | Nivolumab + Ipilimumab | Nivolumab + Ipilimumab vs. Chemotherapy | PD-L1 ≥ 1% | OS: 17.1 months vs. 14.9 months | FDA-approved/2020 |
|  | NEPTUNE Phase III (NCT02542293)359 | Durvalumab + Tremelimumab | Durvalumab + Tremelimumab vs. Chemotherapy | Regardless of PD-L1 levels | OS: 11.7 months vs. 9.1 months (TMB ≥ 20 mut/Mb); 10.9 months vs. 12.1 months (ITT population) |  |
|  | MYSTIC Phase III (NCT02453282)358 | Durvalumab + Tremelimumab | Durvalumab + Tremelimumab vs. Chemotherapy | PD-L1 ≥ 25% | OS: 11.9 months vs. 12.9 months PFS: 3.9 months vs. 5.4 months |  |
Enhanced combination therapy (four-drug regimen) | IMPOWER150 Phase III (NCT02366143)364 | Atezolizumab + Carboplatin + Paclitaxel + Bevacizumab (Non-squamous) | Atezolizumab + Carboplatin + Paclitaxel + Bevacizumab (ABCP) vs. Atezolizumab + Carboplatin + Paclitaxel (ACP) vs. Bevacizumab + Carboplatin + Paclitaxel (BCP) | Regardless of PD-L1 levels | OS: 19.2 months (ABCP) vs. 14.7 months (BCP) PFS: 8.3 months (ABCP) vs. 6.8 months (BCP) | FDA-approved/2018 |
| Â | ORIENT-31 Phase III (NCT03802240)424 | Sintilimab + IBI305 (bevacizumab biosimilar) + Chemotherapy (EGFR-TKI failure) | Sintilimab + IBI305 + Chemotherapy vs. Sintilimab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | PFS: 7.2 months vs. 5.5 months vs. 4.3 months | NMPA-approved/2023 (EGFR-TKI failure) |
| Â | CHECKMATE 9LA Phase III (NCT03215706)860 | Nivolumab + Ipilimumab + Chemotherapy | Nivolumab + Ipilimumab + two cycles of Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | OS: 14.1 months vs. 10.7 months PFS: 6.8 months vs. 5.0 months | FDA-approved/2020 |
| Â | POSEIDON Phase III (NCT03164616)354 | Durvalumab + Tremelimumab + Chemotherapy | Durvalumab + Tremelimumab + Chemotherapy vs. Chemotherapy | Regardless of PD-L1 levels | OS: 14.0 months vs. 11.7 months PFS: 6.2 months vs. 4.8 months | FDA-approved/2022 |
| Â | CCTG BR34 Phase II (NCT03057106)861 | Durvalumab + Tremelimumab + Chemotherapy | Durvalumab + Tremelimumab + Chemotherapy vs. Durvalumab + Tremelimumab | Regardless of PD-L1 levels | OS: 16.6 months vs. 14.1 months PFS: 7.7 months vs. 3.2 months | Â |
