First-Line Nivolumab Monotherapy and Nivolumab plus Ipilimumab in Patients with Advanced NSCLC (CheckMate 012)
In this phase 1b study, 77 patients with squamous and nonsquamous advanced chemotherapy-naive non–small-cell lung cancer (NSCLC) were treated with nivolumab monotherapy (3 mg/kg IV every 2 weeks) or nivolumab combined with ipilimumab (1 mg/kg IV every 6 weeks [Q6W] or every 12 weeks [Q12W]) until disease progression or unacceptable toxicity. PD-L1 expressors >1% and nonexpressors <1% were enrolled. Safety, objective response rate (ORR), and 24-week progression-free survival (PFS) rate were key study end points. Overall survival (OS) was an exploratory end point.
Treatment-related adverse events (AEs; any grade) were reported in 73%, 84%, and 74% of the nivolumab monotherapy, combination Q12W, and combination Q6W cohorts, respectively. Rates of grade 3/4 AEs were 19%, 42%, and 31% for these cohorts, respectively. AEs led to discontinuation in 18% of patients receiving nivolumab plus ipilimumab. Common treatment-related AEs with potential immunologic causes by category included skin, endocrine, and gastrointestinal.
After median follow-up of 16 months for patients in both the nivolumab plus ipilimumab arms of this study, median PFS was 8.0 months (95% confidence interval [CI], 4.1-13.2). In 46 patients with PD-L1 expression ≥1%, median PFS was 12.7 months (95% CI, 7.8-23.0). The 1-year OS rate was 76% for patients in the combination cohorts. The confirmed ORR associated with combination therapy was 43%, which compares favorably with the ORR reported with nivolumab monotherapy; 23% (n = 52).
Researchers concluded that these updated results from CheckMate 012 are promising. The combination of nivolumab and ipilimumab is currently being evaluated in CheckMate 227, a phase 3 study that is enrolling patients who require first-line therapy for advanced NSCLC.
Gettinger SN, et al. WCLC 2016. Abstract OA 03.01. ID 5364.