Immunotherapy combination beneficial for patients with lung cancer with a high tumor mutation burden.
Bristol-Myers Squibb (BMS) recently announced that the ongoing phase 2 CheckMate-227 clinical trial met its primary endpoint of superior progression free survival (PFS) of nivolumab (Opdivo) plus ipilimumab (Yervoy) compared with chemotherapy in patients with non-small cell lung cancer (NSCLC) whose tumors have high tumor mutation burden (TMB), according to a company press release.
TMB is a biomarker that reflects the number of mutations carried by cancer cells and can predict whether a patient will respond to immunotherapy. Tumor cells with high TMB have higher levels of neoantigens, which may help the immune system fight cancer, according to the release.
The researchers evaluated TMB through the FoundationOne CDx assay, which was recently approved by the FDA.
The Data Monitoring Committee recommended that the study continue based on an interim analysis for overall survival (OS), according to BMS.
Notably, the safety profile was consistent with previous findings in NSCLC for nivolumab 3-mg/kg every 2 weeks and low-dose ipilimumab every 6 weeks, according to the release.
“TMB has emerged as an important biomarker for the activity of immunotherapy. For the first time, this phase 3 study shows superior PFS with first-line combination immunotherapy in a predefined population of NSCLC patients with high TMB,” said investigator Matthew D. Hellmann, MD. “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.”
Included in CheckMate-277 were more than 2500 patients with NSCLC randomized to receive nivolumab-based treatments or platinum-doublet chemotherapy. The new findings were across all arms of the Part 1 program.
The 2 co-primary endpoints in the program for the nivolumab-ipilimumab combination were OS among patients whose tumors express PD-L1 and PFS in patients with high TMB, regardless of PD-L1 expression, according to the release.
The researchers found that 45% of TMB-evaluable patients had tumors that had high TMB expression.
“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 chief executive officer, Bristol-Myers Squibb. “These findings attest to our deep understanding of cancer biology, leading translational medicine capabilities and commitment to developing new approaches for cancer patients.”
BMS last week announced positive findings from the phase 2 CheckMate-142 clinical trial, which evaluated the nivolumab-ipilimumab combination in patients with DNA mismatch repair deficient or microsatellite instability-high metastatic colorectal cancer. The trial met its primary endpoint of objective response rate in these patients.