Patients with advanced non-small cell lung cancer (NSCLC) whose tumors have high mutation burden lived longer without the disease progressing when receiving Opdivo (nivolumab) plus Yervoy (ipilimumab), compared to chemotherapy, a Phase 3 trial shows.
The pivotal CheckMate-227 study assessed the treatment as a first-line therapy. The results were independent of PD-L1 expression, a marker that often is used to predict responses to immune checkpoint inhibitors.
Based on an interim analysis for overall survival in patients whose tumors express PD-L1 — the study’s co-primary goal — the Data Monitoring Committee recommended that the study continue.
“TMB [tumor mutation burden] has emerged as an important biomarker for the activity of immunotherapy. For the first time, this Phase 3 study shows superior PFS [progression-free survival] with first-line combination immunotherapy in a predefined population of NSCLC patients with high TMB,” Matthew D. Hellmann, MD, study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center, said in a press release.
The CheckMate-227 study(NCT02477826), currently recruiting participants, has enrolled more than 2,500 patients with advanced NSCLC, including non-squamous and squamous types. The study was set to show that first-line treatment with an Opdivo-based regimen is better than chemotherapy in advanced NSCLC patients.
The trial is divided in three parts — Parts 1a, 1b and 2 — each comparing specific treatment regimens.
In Part 1a, researchers are comparing the Opdivo-Yervoy combo and Opdivo alone with chemotherapy in patients with PD-L1-positive tumors. In Part 1b, Opdivo-Yervoy and Opdivo-chemotherapy combinations are being compared to chemotherapy alone in patients with PD-L1-negative tumors.
The main goals of Part 1 were to determine if Opdivo and Yervoy improved overall survival compared to chemotherapy in patients whose tumors expressed PD-L1, and if the regimen delayed disease progression in patients with high tumor burden, independent of their PD-L1 expression. High tumor burden is measured by the number of gene mutations in a tumor.
Part 2 will evaluate a combination of Opdivo and chemotherapy versus chemotherapy alone in a broad population of patients. The main outcome is overall survival.
Bristol-Myers is collaborating with Foundation Medicine and may soon seek regulatory approval for a companion diagnostic test, called FoundationOne CDx, that assesses a tumor’s mutational burden to identify NSCLC patients most likely to respond to Opdivo plus Yervoy as first-line treatment.
“CheckMate-227 showed that TMB 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,” Hellmann added.
“We believe these data from CheckMate-227 are a breakthrough in cancer research and a meaningful step forward in determining which first-line lung cancer patients may benefit most from the combination of Opdivo and Yervoy,” said Giovanni Caforio, MD, chairman and CEO, Bristol-Myers Squibb.