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Table 3 Registration trials leading to the FDA approval of PD-1/PD-L1 inhibitors in lung cancer

From: Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations

Study/Agent

Tumor (n)

Line of therapy

Experimental arm

Control arm

Primary endpoint

Ref

KEYNOTE-001 (phase Ib)/pembrolizumab

Advanced NSCLC (n = 550)

PD-L1 positive (≥1%) progressing after platinum-based therapy

Pembrolizumab 2 mg/kg every 3 weeks OR 10 mg/kg every 2 or 3 weeks

 

ORR 28% (95% CI 12.1-49.4%) vs. 40% (95% CI 22.4-61.2) vs. 41% (95% CI 24.7-59.3%) for PD-L1 ≥ 50%

OS 22.1 mo (treatment-naïve, 95% CI 17.1-27.2) vs. 10.6 mo (previously-treated, 95% CI 8.6-13.3) for PD-L1 ≥ 50%

21, 22

KEYNOTE-024 (phase III)/pembrolizumab

Metastatic NSCLC with ≥50% PD-L1 expression (n = 305)

First-line

Pembrolizumab 200 mg every 3 weeks

ICC (cisplatin/carboplatin + pemetrexed, cisplatin/carboplatin + gemcitabine, or carboplatin + paclitaxel)

PFS 10.3 mos vs. 6.0 mos (HR 0.50, 95% CI 0.37-0.68, p < 0.001)

25

KEYNOTE-021 (phase II)/pembrolizumab

Advanced NSCLC (n = 123)

First line (in combination with platinum-doublet chemotherapy)

Pembrolizumab 200 mg + carboplatin AUC 5 mg/ml/min + pemetrexed 500 mg/m2 every 3 weeks X4 cycles followed by pembrolizumab (24 months duration) and indefinite maintenance pemetrexed

Carboplatin + pemetrexed X4 cycles followed by indefinite maintenance pemetrexed

ORR 55% vs. 29% (estimated treatment difference of 26%, 95% CI 9-42%, p = 0.0016)

26

CheckMate 017 (phase III)/nivolumab

Metastatic squamous NSCLC (n = 272)

Previously treated with platinum-based chemo

Nivolumab 3 mg/kg every 2 weeks

Docetaxel 75 mg/m2 every 2 weeks

OS 9.2 mo vs. 6.0 mos (HR 0.59, 95% CI 0.44-0.79, p < 0.001)

27

CheckMate 057 (phase III)/nivolumab

Metastatic non-squamous NSCLC (n = 582)

Previously treated with platinum-based chemo

Nivolumab 3 mg/kg every 2 weeks

Docetaxel 75 mg/m2 every 3 weeks

OS 12.2 mos vs. 9.4 mos (HR 0.73, 96% CI 0.59-0.89, p = 0.002)

28

POPLAR (phase II)/OAK (phase III)/atezolizumab

NSCLC (POPLAR n = 287, OAK n = 1225)

Second-line

Atezolizumab 1200 mg every 3 weeks

Docetaxel 75 mg/m2

POPLAR: OS 12.6 mos vs. 9.7 mos (HR 0.7, 95% CI 0.53-0.99, p = 0.04)

OAK: OS 13.8 mos vs. 9.6 mos (HR 0.73, 95% CI 0.62-0.87, p = 0.0003)

29, 30

  1. FDA Food and Drug Administration, PD-1 programmed cell death 1, PD-L1 programmed death ligand 1, NSCLC non-small cell lung cancer, ORR overall response rate, CI confidence interval, OS overall survival, ICC investigator-choice chemotherapy, PFS progression-free survival, HR hazard ratio, AUC area under curve
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