Results for CHECKMATE 227 study of Opdivo and Yervoy combination for NSCLC in patients with high tumor mutational burden. BMS.

Results from its CheckMate-227 study of combination Yervoy and Opdivo from BMS in first-line NSCLC show that inhibiting both checkpoint molecules can help delay disease worsening or death over chemotherapy. A progression-free survival benefit was most pronounced, , in a subset of patients who had high tumor mutational burden (TMB), another biomarker designed to identify those most likely to benefit.Patients with greater than 10 mutations per megabase � a cutoff which includes about 45% of NSCLC patients without EGFR or ALK mutations � were 42% less likely to see their cancer progress than those who received platinum-doublet chemotherapy.

Tumor mutation burden, or TMB, is a quantitative biomarker that reflects the total number of mutations carried by tumor cells. Tumor cells with high TMB have higher levels of neoantigens, which are thought to help the immune system recognize tumors and incite an increase in cancer-fighting T cells and an anti-tumor response. TMB is one type of biomarker that may help predict the likelihood a patient responds to immunotherapies.

Across all randomized patients on the study, the relative risk reduction from treatment reported in at a more modest 17% due to worse performance by those patients below the TMB cutoff. For TMB-low patients, treatment with chemotherapy actually resulted in better results. Overall survival data remained immature at the time of analysis, while median progression free survival among TMB high patients was 7.2 months on treatment versus 5.5 months on chemoherapy. Bristol-Myers expects data on overall survival by PD-L1 expression to come in late 2018 or early 2019, after which a submission to regulators could follow if the data remains positive.