Table 5.
Clinical trials of anti-programmed death-1 and anti-programmed death-ligand 1 in non-small-cell lung cancer.
| Trial | Drug/dose | Patients | Grade 3–4 toxicities (n, %) | Overall response rate (%) | PFS (%) | OS (%) | Ref. |
|---|---|---|---|---|---|---|---|
| A Phase I study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) plus platinum-based doublet chemotherapy (PT doublet) in chemotherapy-naive NSCLC patients (Rizvi et al., 2013)† | Nivolumab/10 mg/kg every 3 weeks | 43 patients with NSCLC who had failed ≥1 chemotherapy regimen (arm A: squamous; arm B: nonsquamous; arm C: combination) | Any grade 3–4 toxicity (21, 49) Pneumonitis (3, 7) Rash (2, 5) Nephritis (1, 2) Colitis (1, 2) |
Arm A: 33 Arm B: 33 Arm C: 31 |
Not reported | Not reported | [55] |
| Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic NSCLC (Spigel et al., 2013)† | MPDL3280A/1–20 mg/kg every 3 weeks | 53 patients with advanced NSCLC evaluable at time of presentation | Any grade 3–4 toxicity (34%) Pericardial effusion (6%) Dehydration (4%) Dyspnea (4%) Fatigue (4%) |
Of 37 patients reported (24) PD-L1+ (100) PD-L1− (15) |
At 24 weeks: 48 | Not reported | [56] |
| Survival and long-term follow-up of the Phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with previously treated advanced NSCLC (Brahmer et al., 2013)† | Nivolumab/1, 3 or 10 mg/kg every 2 weeks | 127 patients with advanced NSCLC evaluable at time of presentation | Fatigue Pneumonitis (2%) AST elevation (2%) |
Of 122 patients reported (16) Nonsquamous (15) Squamous (19) |
Not reported | Squamous at 1 year (44) Squamous at 2 years (44) Nonsquamous at 1 year (41) Nonsquamous at 2 years (17) |
[50] |
| Preliminary clinical safety and activity of MK-3475 monotherapy for the treatment of previously treated patients with NSCLC (Garon et al., 2013) | MK-3475 10 mg/kg every 3 weeks | 38 patients with advanced NSCLC | Pulmonary edema (1, 3) | Overall: 24 (by irIC) 21 (by RECIST v1.1) PD-L1 high: 67 (by irIC) 57 (by RECIST v1.1) PD-L1 low: 4 (by irIC) 9 (by RECIST v1.1) |
Not yet reported | Not yet reported | [51] |
| Clinical activity, safety and biomarkers of PD-L1 blockade in non-small-cell lung cancer (NSCLC) (Soria et al., 2013) | MPDL3280A intravenously every 3 weeks | 85 patients with advanced NSCLC | Pericardial effusion (6%) Dehydration (4%) Dyspnea (4%) Fatigue (4%) |
Overall (23) PD-L1 intermediate (46) PD-L1 high (83) Smokers (26) Nonsmokers (10) |
At 24 weeks: Squamous: 44 Nonsquamous: 46 |
Not yet reported | [52] |
†
American Society of Clinical Oncology 2013 abstract.
AST: Aspartate aminotransferase; irlC: Immune-related response criteria; NSCLC: Non-small-cell lung cancer; OS: Overall survival; PD-1: programmed death-1; PD-L1: Programmed PFS: Progression-free survival; PT: Platinum; RECIST: Response Evaluation Criteria in Solid Tumors.