Bristol-Myers Squibb Company announced that the European Medicines Agency (EMA) validated a type II variation application for the Opdivo (nivolumab) plus Yervoy (ipilimumab) combination for treatment in adult patients with first-line metastatic non-small cell lung cancer (NSCLC) who have tumor mutational burden (TMB) =10 mutations/megabase (mut/Mb). Validation of the application confirms the submission is complete and begins the EMA’s centralised review process.

Sabine Maier, M.D., development lead, thoracic cancers, Bristol-Myers Squibb, commented, “Europe has one of the highest incidence rates of advanced lung cancer, currently accounting for 20% of all cancer deaths. The Opdivo plus low-dose Yervoy combination has the potential to offer first-line NSCLC patients with TMB =10 mut/Mb a chemotherapy-sparing I-O/I-O regimen. The validation of our application by the EMA is a step forward in the regulatory review process, and we will continue to work with urgency to bring precision immunotherapy to patients with lung cancer in the European Union.”

The application is based on data from Part 1 of CheckMate -227, a global Phase 3 study evaluating Opdivo-based regimens versus chemotherapy in patients with first-line advanced NSCLC across squamous and non-squamous histologies. Initial results from this study were presented at the American Association for Cancer Research Annual Meeting in April 2018 and simultaneously published in The New England Journal of Medicine.

CheckMate -227 is an open-label Phase 3 trial evaluating Opdivo-based regimens versus platinum-doublet chemotherapy in patients with first-line advanced non-small cell lung cancer (NSCLC) across non-squamous and squamous tumor histologies.

This programme is comprised of three parts:

Part 1a: Opdivo plus low-dose Yervoy or Opdivo monotherapy versus chemotherapy in patients whose tumors express PD-L1.

Part 1b: Opdivo plus low-dose Yervoy or Opdivo plus chemotherapy versus chemotherapy in patients whose tumors do not express PD-L1.

Part 2: Opdivo plus chemotherapy versus chemotherapy in a broad population, regardless of PD-L1 or TMB status.

There are two co-primary endpoints in Part 1 for the Opdivo plus Yervoy combination (versus chemotherapy): overall survival (OS) in patients whose tumors express PD-L1 (assessed in patients enrolled in Part 1a, which is ongoing and continues to final analysis) and progression-free survival (PFS) in patients with tumor mutational burden (TMB) =10 mut/Mb across the PD-L1 spectrum (assessed in patients enrolled across Parts 1a and 1b). The primary endpoint in Part 2 is OS.

In Part 1 of this study, patients were randomised 1:1:1 to Opdivo 3 mg/kg every two weeks plus low-dose Yervoy 1 mg/kg every six weeks; histology-based platinum-doublet chemotherapy every three weeks for up to four cycles; and Opdivo 240 mg every two weeks (Part 1a) or Opdivo 360 mg plus histology-based platinum-doublet chemotherapy every three weeks for up to four cycles, followed by Opdivo monotherapy (Part 1b).

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 recognise 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.

Lung cancer is the leading cause of cancer deaths globally, resulting in nearly 1.7 million deaths each year, according to the World Health Organisation In Europe alone, lung cancer is responsible for an estimated 353,000 deaths from the disease every year – more than breast cancer, colorectal and prostate cancers combined.Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer and accounts for approximately 85% of diagnoses. About 25% to 30% of all lung cancers are squamous cell carcinomas, and non-squamous NSCLC accounts for approximately 50% to 65% of all lung cancer diagnoses. Survival rates vary depending on the stage and type of the cancer when diagnosed.

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers. Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.