Six-year results from Part 1 of the Phase III CheckMate-227 trial continue to demonstrate long-term, durable survival benefits of nivolumab plus ipilimumab compared to chemotherapy in the first-line treatment of patients with metastatic non-small cell lung cancer (mNSCLC), regardless of PD-L1 expression levels. Follow-up results were presented in an oral presentation at the IASLC 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (Abstract OA14.03).
With a minimum follow-up of over 6 years (73.5 months), the longest reported for a Phase III trial with immunotherapy in mNSCLC, follow-up results of the primary endpoint population of patients with tumor PD-L1 expression >=1 percent show that the 6-year survival rate for nivolumab plus ipilimumab was 22 percent, compared to 13 percent for chemotherapy (HR: 0.78; 95% CI: 0.67-0.91).
In an exploratory analysis of patients with PD-L1 expression <1 percent, more than 3 times as many patients treated with nivolumab plus ipilimumab were alive at 6 years compared to those treated with chemotherapy (16% vs. 5%, respectively; HR 0.65; 95% CI: 0.52-0.81).
Among those who responded to treatment, greater proportions of patients had tumor burden reduction >=80 percent with nivolumab plus ipilimumab versus chemotherapy in both the PD-L1 >=1 percent (15% vs. 3%, respectively) and <1 percent (8% vs. 1%, respectively) subgroups, and 6-year overall survival (OS) rates for patients with tumor burden reduction >=80 percent with nivolumab plus ipilimumab were higher compared to chemotherapy (59% vs. 42% for PD-L1 >=1% and 77% vs. 0% for PD-L1 <1%, respectively).
The safety profile for the dual immunotherapy combination nivolumab plus ipilimumab remained consistent with previously reported data from this trial and was manageable with established protocols, with no new safety signals identified.
"Immunotherapy has transformed the treatment of advanced lung cancer and, thankfully, a diagnosis no longer means the same thing as it used to for many patients. With these 6-year results, we are seeing remarkably sustained and durable clinical survival benefits with nivolumab plus ipilimumab year-over-year," said Solange Peters, MD, PhD, Professor and Chair of Medical Oncology and the Thoracic Malignancies Program in the Department of Oncology at the University Hospital of Lausanne in Lausanne, Switzerland. "The long-term efficacy seen with the dual immunotherapy regimen in CheckMate-227 reinforces the importance of nivolumab plus ipilimumab to transform outcomes for appropriate patients with metastatic non-small cell lung cancer."
Nivolumab plus ipilimumab-based combinations have shown significant improvements in OS in six Phase III clinical trials in five tumors to date: metastatic NSCLC, metastatic melanoma, advanced renal cell carcinoma, malignant pleural mesothelioma, and esophageal squamous cell carcinoma.
About CheckMate-227
CheckMate-227 is a multi-part open-label global randomized Phase III trial evaluating nivolumab-based regimens versus platinum-doublet chemotherapy in patients with first-line mNSCLC across non-squamous and squamous tumor histologies. There are two independent primary endpoints in Part 1 for nivolumab plus ipilimumab (versus chemotherapy): 1) overall survival (OS) in patients whose tumors express PD-L1 (assessed in patients enrolled in Part 1a) and 2) progression-free survival (PFS) in patients with tumor mutational burden (TMB) >=10 mutations/megabase (mut/Mb) across the PD-L1 spectrum (assessed in patients enrolled across Parts 1a and 1b). Patients were treated as follows:
* Part 1a: Nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks), nivolumab monotherapy (240 mg every 2 weeks), or chemotherapy (every 3 weeks for up to 4 cycles) in patients whose tumors express PD-L1 (>=1%)
* Part 1b: Nivolumab plus ipilimumab, nivolumab (360 mg every 3 weeks) plus chemotherapy (every 3 weeks for up to 4 cycles), or chemotherapy (every 3 weeks for up to 4 cycles) in patients whose tumors do not express PD-L1 (<1%)
Part 1 met both its independent primary endpoints of PFS with the nivolumab plus ipilimumab combination versus chemotherapy in patients whose tumors have high (>=10 mut/Mb) TMB, regardless of PD-L1 expression, and OS demonstrating a superior benefit for nivolumab plus ipilimumab versus chemotherapy in first-line metastatic NSCLC patients whose tumors expressed PD-L1 >=1 percent.