Table 2. Registration trials for single-agent immunotherapy in NSCLC.
| Immunotherapy agent | Mechanism of action | Treatment regimen | Trial description | Enrollment number | Trial status | NCT number/reference |
|---|---|---|---|---|---|---|
| Nivolumab | Anti-PD-1 human MoAb | Nivolumab 3 mg/kg IV Q2W | Phase: phase 3 RCT; indication: treatment naïve PD-L1 positive (≥5% expression) EGFR wild-type stage IV/recurrent NSCLC without ALK translocation; treatment arms: (I) experimental arm: nivolumab 3 mg/kg IV Q2W; (II) active comparator: 6 cycles of investigators’ choice of platinum-based chemotherapy; results: median PFS: (I) nivolumab arm: 4.2 months; (II) chemotherapy arm: 5.9 months; grade 3–4 TRAE: (I) nivolumab arm: 18%; (II) chemotherapy arm: 51% | 541 | Closed; follow-up for survival data | NCT02041533; CheckMate 026 (55) |
| Pembrolizumab (MK-3475) | Anti-PD-1 human MoAb | Pembrolizumab 200 mg IV Q3W | Phase: phase 3 RCT; indication: patients with PD-L1 positive, ALK negative, EGFR negative NSCLC; treatment arms: patients randomized to receive platinum doublet chemotherapy for 6 cycles or pembrolizumab for a maximum of 35 cycles as first-line therapy; primary endpoint: OS of participants with strong PD-L1 positivity; secondary endpoints: PFS of participants with strong PD-L1 positivity; PFS and OS of all study participants | 1,240 | Active, not recruiting | NCT02220894; KEYNOTE 042 (56) |
| Pembrolizumab (MK-3475) | Anti-PD-1 human MoAb | Pembrolizumab 200 mg IV Q3W | Phase: phase 3 RCT; indication: Patients with non-squamous NSCLC that are not eligible for anti-EGFR/ALK mutation targeted therapy; treatment arms: (I) experimental arm: 4 cycles of pembrolizumab 200 mg Q3W plus chemotherapy (pemetrexed 500 mg/m2 and carboplatin AUC 5 or cisplatin 75 mg/m2 Q3W) followed by pemetrexed 500 mg/m2 Q3W plus pembrolizumab 200 mg Q3W; (II) control arm: placebo plus chemotherapy Q3W followed by pemetrexed 500 mg/m2 plus placebo Q3W; primary endpoint: PFS; secondary endpoints: safety, duration of response, OS, ORR, PFS for study participants with a PD-L1 expression TPS score ≥1% | 570 | Active, not recruiting | NCT02578680; KEYNOTE 189 (57) |
| Pembrolizumab (MK-3475) | Anti-PD-1 human MoAb | Pembrolizumab 200 mg IV Q3W | Phase: phase 3 RCT; indication: treatment naïve stage IV squamous NSCLC; treatment arms: (I) experimental arm: pembrolizumab 200 mg Q3W for a maximum of 35 cycles plus chemotherapy (4 cycles of carboplatin AUC 6 Q3W plus paclitaxel 200 mg/m2 or nab-paclitaxel 100 mg/m2 on days 1, 8, 15); (II) control arm: placebo (normal saline) Q3W for a maximum of 35 cycles plus chemotherapy; primary endpoint: PFS, OS (assessed up to 2 years); secondary endpoints: ORR (assessed up to 2 years) | 560 | Recruiting | NCT02775435; KEYNOTE 407 |
| Atezolizumab (MPDL3280A) | Anti-PD-L1 MoAb | Atezolizumab 1,200 mg IV Q3W | Phase: phase 3 RCT; indication: chemotherapy naïve stage IV non-squamous NSCLC; treatment arms: (I) experimental arm 1: Atezolizumab 1,200 mg IV Q3W plus chemotherapy (4 or 6 cycles of nab-paclitaxel 100 mg/m2 on day 1, 8 and 15 plus carboplatin AUC 6 Q3W); (II) control arm: chemotherapy only; primary endpoint: investigator assessed PFS using RECIST v1.1 (assessed up to 2.5 years); secondary endpoints: duration of response, objective response, PFS (evaluated by an independent review facility), OS (assessed up to 3.5 years), safety, changes in patient-reported cancer symptoms from baseline and TTD | 650 | Recruiting | NCT02366143; IMpower 130 (58) |
| Atezolizumab (MPDL3280A) | Anti-PD-L1 MoAb | Atezolizumab 1,200 mg IV Q3W | Phase: phase 3 RCT; indication: treatment naïve stage IV squamous NSCLC; treatment arms: (I) experimental arm 1: Atezolizumab 1,200 mg IV Q3W plus chemotherapy (4 or 6 cycles of nab-paclitaxel 100 mg/m2 on day 1, 8 and 15 plus carboplatin AUC 6 Q3W); (II) experimental arm 2: Atezolizumab plus chemotherapy (4 or 6 cycles of paclitaxel 200 mg/m2 plus carboplatin AUC 6 Q3W); (III) comparator arm: chemotherapy only (carboplatin plus nab-paclitaxel); primary endpoint: Investigator assessed PFS using RECIST v1.1 (evaluated up to 28 months), OS (evaluated up to 44 months); secondary endpoints: duration of response, objective response, PFS (evaluated by an independent review facility), TTR, TIR, incidence of AE, percent patients with anti-therapeutic antibody response to atezolizumab, changes in patient-reported cancer symptoms from baseline and TTD | 1,025 | Recruiting | NCT02367794; IMpower 131 (58) |
| Atezolizumab (MPDL3280A) | Anti-PD-L1 MoAb | Atezolizumab 1,200 mg IV Q3W | Phase: phase 3 RCT; indication: treatment naïve stage IV non-squamous NSCLC; treatment arms: (I) experimental arm 1: Atezolizumab 1,200 mg IV Q3W plus chemotherapy (4 or 6 cycles of paclitaxel 200 mg/m2 plus carboplatin AUC 6 Q3W); (II) experimental arm 2: Atezolizumab 1,200 mg IV Q3W plus chemotherapy and bevacizumab 15 mg/kg IV Q3W; (III) control arm: bevacizumab plus chemotherapy; primary endpoint: investigator assessed PFS using RECIST v1.1 (assessed up to 2 years); secondary endpoints: objective response, duration of response, PFS (evaluated by an independent review facility), OS (assessed up to 7 years), safety, changes in patient-reported cancer symptoms from baseline and TTD | 1,200 | Recruiting | NCT02366143; IMpower 150 (58) |
| Avelumab (MSB0010718C) | Anti-PD-L1 MoAb | Avelumab 10 mg/kg IV over 60 minutes Q2W | Phase: phase 3 RCT; indication: treatment naïve stage IV/recurrent PD-L1 positive NSCLC; treatment arms: (I) experimental arm 1: avelumab 10 mg/kg IV Q2W; (II) experimental arm 2: avelumab 10 mg/kg once a week for 12 weeks, later continued as Q2W till unacceptable toxicity or progression of disease; (III) active comparator arm: Platinum base chemotherapy for a maximum of 6 cycles; non-squamous NSCLC: pemetrexed 500 mg/m2 Q3W plus cisplatin 75 mg/m2 Q3W or pemetrexed 500 mg/m2 Q3W plus carboplatin AUC 6 mg/mL/min Q3W; squamous NSCLC: paclitaxel 200 mg/m2 Q3W plus carboplatin AUC 6 mg/mL/min Q3W, gemcitabine 1,000 mg/m2 on day 1, 8 of 3 weeks cycle plus carboplatin AUC 5 mg/mL/min Q3W or gemcitabine 1,250 mg/m2 on day 1, 8 of 3 weeks cycle plus cisplatin 75 mg/m2 Q3W; primary endpoint: PFS and OS for high PD-L1 expression tumors; secondary endpoint: PFS and OS for patients with high, moderate or any PD-L1 expression, duration of response, best overall response, change from baseline in EORTC QLQ-LC13, EORTC QLQ-C30 global health status and EQ-5D-5L health outcome questionnaire, number of patients with abnormal 12-lead ECG, ECOG performance status, treatment-emergent adverse events, vital signs, physical examination and safety laboratory tests graded by NCI-CTCAE | 1,095 | Recruiting | NCT02576574; JAVELIN lung 100 study |
| Avelumab (MSB0010718C) | Anti-PD-L1 MoAb | Avelumab 10 mg/kg IV over 60 minutes Q2W | Phase: phase 3 RCT; indication: PD-L1 positive NSCLC presenting with progression of disease after or during prior treatment with platinum doublet chemotherapy; treatment arms: (I) experimental arm: Avelumab 10 mg/kg IV Q2W; (II) comparator arm: Docetaxel 75 mg/m2 Q3W; (III) primary endpoint: OS, evaluated for a maximum of 7.6 years; secondary endpoint: PFS, best overall response, change from baseline in EORTC QLQ-LC13, EORTC QLQ-C30 global health status and EQ-5D-5L health outcome questionnaire, number of patients with treatment-emergent adverse events as graded by NCI-CTCAE |
792 | Active, not recruiting | NCT02395172; JAVELIN lung 200 study |
| Durvalumab MEDI4736 | anti-PD-L1 MoAb | NA | Phase: phase 3 RCT; indication: treatment naïve advanced NSCLC with high PD-L1 expression (≥25% staining) treatment arms: (I) experimental arm: durvalumab monotherapy; (II) active comparator: standard of care platinum-based chemotherapy (pemetrexed/cisplatin, pemetrexed/carboplatin, gemcitabine/cisplatin, gemcitabine/carboplatin); primary endpoint: PFS and OS; secondary endpoint: duration of response, ORR, PFS at 12 months, health-related quality of life as per EORTC QLQ-C30 questionnaire, cancer-related symptoms as per EORTC QLQ-LC13 questionnaire, determine immunogenicity of durvalumab by measurement of anti-drug antibodies, incidence of TRAEs | 440 | Recruiting | NCT03003962; PEARL trial |
MoAb, monoclonal antibody; PD-1, programmed cell death receptor-1; PD-L1, programmed cell death ligand-1; AUC, area under concentration curve; RCT, randomized control trial; NSCLC, non-small cell lung cancer; PFS, progression free survival; OS, overall survival; ORR, objective response rate; TPS, tumor proportion score; TTD, time to deterioration; TTR, time to response; TIR, time in response; AE, adverse events; TRAE, treatment-related adverse events; EORTC QLQ-C30, European Organization for the Research and Treatment of Cancer Quality of Life; EQ-5D-5L, European Quality of Life 5-dimensions; EORTC QLQ-LC13, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13; ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events.