The ongoing phase III CheckMate-227 study met its coprimary endpoint of progression-free survival with a combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) vs chemotherapy in patients with first-line advanced non–small cell lung cancer (NSCLC) whose tumors have a high (≥ 10 mutations/megabase) tumor mutation burden, regardless of programmed cell death ligand 1 (PD-L1) expression. In the study, tumor mutation burden was evaluated using the analytically validated assay FoundationOne CDx.
Additionally, based on an interim analysis for overall survival, the Data Monitoring Committee recommended that the study continue. The safety profile was consistent with previously reported findings in first-line NSCLC for the combination schedule of nivolumab at 3 mg/kg every 2 weeks and low-dose ipilimumab (1 mg/kg) every 6 weeks.
“Tumor mutation burden has emerged as an important biomarker for the activity of immunotherapy. For the first time, this phase III study shows superior progression-free survival with first-line combination immunotherapy in a predefined population of NSCLC patients with high tumor mutation burden,” said Matthew D. Hellmann, MD, study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center. “CheckMate-227 showed that tumor mutation burden is an important, independent predictive biomarker that can identify a population of first-line NSCLC patients who may benefit from the nivolumab-plus-ipilimumab combination.”
CheckMate-227 is an open-label phase III trial with more than 2,500 patients randomized across nonsquamous and squamous histologies, evaluating nivolumab-based regimens vs platinum-doublet chemotherapy in patients with first-line advanced NSCLC. This large program comprises three parts—parts 1a and 1b, and part 2.
Part 1a is evaluating nivolumab plus ipilimumab and nivolumab monotherapy vs chemotherapy in patients whose tumors express PD-L1. Part 1b evaluated nivolumab plus ipilimumab and nivolumab plus chemotherapy vs chemotherapy in patients whose tumors do not express PD-L1. PD-L1 expression levels were assessed using the Dako-developed diagnostic PD-L1 IHC 28-8 pharmDx.
This announcement is based on an analysis of patients from the nivolumab-plus-ipilimumab arms and chemotherapy arms across all of part 1. There are two coprimary endpoints in part 1 for the nivolumab plus ipilimumab combination: overall survival in patients whose tumors express PD-L1 (assessed in patients enrolled in part 1a) and progression-free survival in patients with high tumor mutation burden, regardless of PD-L1 expression (assessed in patients enrolled across parts 1a and 1b). Approximately 45% of the tumor mutation burden–evaluable patients had tumors that expressed high tumor mutation burden (≥ 10 mutations/megabase) in the study.
Part 2 is evaluating nivolumab plus chemotherapy vs chemotherapy in a broad population with a primary endpoint of overall survival.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.