Results from Part 1 of the phase 3 CheckMate -227 trial showed that treatment with nivolumab, a human programmed death receptor-1 (PD-1)-blocking antibody, plus low-dose ipilimumab, a cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody, was associated with superior overall survival (OS) compared with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), regardless of PD-L1 expression level.
CheckMate -227 is a 48-month, open-label trial evaluating nivolumab-based regimens vs platinum-doublet chemotherapy in patients with advanced NSCLC. Patients with tumors expressing PD-L1 were randomized to receive either nivolumab plus low-dose ipilimumab or nivolumab monotherapy vs chemotherapy; patients with tumors not expressing PD-L1 were randomized to receive either nivolumab plus low-dose ipilimumab or nivolumab plus chemotherapy vs chemotherapy. The co-primary end points included OS in patients whose tumors expressed PD-L1 and progression-free survival (PFS) in patients with a tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb) across the PD-L1 spectrum.
Findings from Part 1 of the trial showed that in patients whose tumors expressed PD-L1 ≥1%, nivolumab plus low-dose ipilimumab showed a superior benefit in OS compared with chemotherapy (Hazard Ratio [HR] 0.79; 97.72% CI: 0.65 to 0.96). Further exploratory analysis demonstrated improved OS for nivolumab plus low-dose ipilimumab in patients with PD-L1 <1% (HR 0.62; 95% CI: 0.48 to 0.78).
Treatment with nivolumab plus low-dose ipilimumab also resulted in improved PFS for patients with TMB ≥10mut/Mb, regardless of PD-L1 expression, compared with chemotherapy. Additionally, the combination regimen was associated with a 2-year survival rate of 40% in both patients whose tumors expressed PD ≥1% and PD <1%; in the chemotherapy control group, the 2-year survival rate was 33% and 23%, respectively.
“These positive results validate the immunologic rationale for the dual inhibition of PD-1 and CTLA-4 in the treatment of lung cancer,” said Martin Reck, MD, PhD, CheckMate -227 study investigator, Lung Clinic Grosshansdorf, German Center of Lung Research. “These data show that dual Immuno-Oncology therapy has the potential to deliver deep and durable responses, with a clear survival benefit, in first-line non-small cell lung cancer, without the need for chemotherapy.”
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