Opdivo + chemotherapy and /or Yervoy shows improved PFS in CHECKMATE 227 trial over chemotherapy in first line NSCLC with PD-L1 expression less than 1%.- BMS

Bristol-Myers Squibb Company announced results from a part of the Phase III CheckMate -227 trial that evaluated Opdivo (nivolumab) plus low-dose Yervoy (ipilimumab) and Opdivo plus chemotherapy versus chemotherapy in patients with first-line advanced non-small cell lung cancer (NSCLC) with PD-L1 expression less than 1%, across squamous and non-squamous tumor histologies (Part 1b).

Data show that Opdivo plus chemotherapy (n=177) extended progression-free survival (PFS) versus chemotherapy (n=186) in patients with PD-L1 expression <1% (HR 0.74; 95% CI: 0.58 to 0.94). PFS is a secondary endpoint for Opdivo plus chemotherapy in Part 1b of the study, and results are based on a descriptive analysis. In an exploratory analysis of patients with high tumor mutational burden (TMB) greater than 10 mutations/megabase (mut/Mb) and PD-L1 expression <1%, the one-year PFS rates were 45% with Opdivo plus low-dose Yervoy (n=38), 27% with Opdivo plus chemotherapy (n=43) and 8% with chemotherapy (n=48). In patients with low TMB (<10 mut/Mb) and PD-L1 <1%, the one-year PFS rate was 18% with both Opdivo plus low-dose Yervoy (n=52) and Opdivo plus chemotherapy (n=54) and was 16% with chemotherapy (n=59).

Hossein Borghaei, D.O., study investigator and chief of thoracic medical oncology at Fox Chase Cancer Center in Philadelphia, said, “For the first time, CheckMate -227 allows the oncology community to look at I-O/I-O and I-O/chemotherapy in one data set. Results show Opdivo plus chemotherapy improved progression-free survival versus chemotherapy in first-line lung cancer patients whose tumors do not express PD-L1. Taken together with the totality of CheckMate -227 data presented to date, the results reinforce that TMB (tumour mutational burden) status provides clinically relevant information for Opdivo-based combinations and that Opdivo plus low-dose Yervoy provided durable efficacy in patients with high TMB.”.

Results from Part 1b of CheckMate -227 will be presented during the Lung Cancer—Non-Small Cell Metastatic oral abstract session at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract #9001).

In this report, Grade 3-4 treatment-related adverse events (TRAEs) were observed in 25% of patients who received Opdivo plus low-dose Yervoy, 52% with Opdivo plus chemotherapy and 35% with chemotherapy. The most common select Grade 3-4 TRAEs with Opdivo plus low-dose Yervoy were hepatic (8%), gastrointestinal (3%), endocrine (3%), skin (3%), diarrhea (2%), anemia (2%), fatigue (1%), asthenia (1%) and nausea (1%). The most common Grade 3-4 TRAEs with Opdivo plus chemotherapy were anemia (17%), neutropenia (12%), decreased neutrophil count (10%), fatigue (5%), hepatic (3%), decreased appetite (2%), nausea (2%), gastrointestinal (2%), diarrhea (1%), skin (1%) and endocrine (0.6%).

Comment:Bristol-Myers Squibb’s strategy for lung cancer relies on showing a new biomarker can help predict who benefits most from immunotherapy combinations. As part of the Checkmate-227 study, BMS segmented a group of patients whose tumors do not bear the well-established biomarker PD-L1 to show that combinations featuring its PD-1 drugs Opdivo and Opdivo and Yervoy combination, and Opdivo-plus-chemotherapy—worked better in those with high levels of tumor mutational burden, or TMB.

Tumour Mutational Burden:Over time, cancer cells accumulate mutations that are not seen in normal cells of the body. Tumor mutational 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.