The majority of patients with non-small cell lung cancer ( NSCLC ) present at the time of diagnosis with advanced disease. Subsets of patients are eligible for therapies targeted at mutated oncogene drivers; however, the majority of patients have few effective options beyond standard Platinum-based chemotherapy.
Preclinical data suggest that immune dysfunction, including T-cell downregulation through increased tumor expression of programmed death-1 ligand ( PD-L1 ), plays a role in non-small cell lung cancer.
Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has shown clinical activity against several solid tumors including non-small cell lung cancer.
Preliminary data suggest that Nivolumab’s activity in first-line non-small cell lung cancer is accentuated in patients with positive tumor PD-L1 expression ( PD-L1+ ).
A phase III, randomized, open-label trial will compare the clinical activity of first-line Nivolumab monotherapy versus investigator's choice chemotherapy ( ICC ) in treatment-naïve patients with stage IV or recurrent non-small cell lung cancer with PD-L1+ tumor expression.
Chemotherapy-naïve patients with ECOG performance status 1 or less and without known EGFR mutations or ALK translocations will be randomized 1:1 to Nivolumab ( 3 mg/kg IV Q2W ) or investigator's choice chemotherapy, and stratified by tumor PD-L1 expression level ( Dako immunohistochemistry assay ) and NSCLC histology.
Patients randomized to investigator's choice chemotherapy ( maximum of six 3-week cycles ) will receive Gemcitabine 1250 mg/m2 + Cisplatin 75 mg/m2, Gemcitabine 1000 mg/m2 + Carboplatin AUC 5, or Paclitaxel 200 mg/m2 + Carboplatin AUC 6 ( squamous ), or Pemetrexed 500 mg/m2 + either Cisplatin 75 mg/m2 or Carboplatin AUC 6; with optional crossover to Nivolumab.
The primary objective is to assess progression-free survival ( PFS ) with Nivolumab versus investigator's choice chemotherapy in patients with strong PD-L1 expression.
Secondary objectives are objective response rate and overall survival in strongly PD-L1+ patients, progression-free survival in patients with any PD-L1 expression level, and disease-related symptom improvement.
Exploratory objectives include safety, correlation of PD-L1 expression with progression-free survival, pharmacokinetics, pharmacodynamics, pt-reported outcomes, and potential biomarkers. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Meeting, 2014