Bristol Myers Squibb Receives European Commission Approval for Opdivo (nivolumab) plus Yervoy (ipilimumab) with Two Cycles of Chemotherapy for First-Line Treatment of Metastatic Non-Small Cell Lung Cancer

Approval based on Phase 3 CheckMate -9LA trial results showing superior overall survival in patients with metastatic non-small cell lung cancer, regardless of PD-L1 expression or tumor histologies

European Commission decision marks the first time a dual immunotherapy with limited chemotherapy is approved for patients with non-small cell lung cancer in the EU

Opdivo plus Yervoy-based combinations now indicated in the EU for three different advanced cancer types: non-small cell lung cancer, melanoma and renal cell carcinoma

PRINCETON, NJ, USA I November 06, 2020 IBristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo (nivolumab) plus Yervoy (ipilimumab) with two cycles of platinum-based chemotherapy for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation. The combination of Opdivo plus Yervoy with two cycles of chemotherapy is the first dual immunotherapy-based treatment option approved for patients in the European Union (EU) with this disease.

The EC’s decision is based on results from the Phase 3 CheckMate -9LA trial, which met its primary endpoint of superior overall survival (OS), as well as secondary endpoints of progression-free survival (PFS) and overall response rate (ORR), for the combination of Opdivo plus Yervoy, given concomitantly with two cycles of chemotherapy, versus chemotherapy alone. An improvement in duration of response (DoR) was also observed. The safety profile of Opdivo plus Yervoy and two cycles of chemotherapy was reflective of the known safety profiles of the immunotherapy and chemotherapy components in first-line NSCLC.

“With a complex disease like metastatic non-small cell lung cancer, the availability of different treatment options is critical for patients, who have diverse needs and challenges,” said Martin Reck, M.D., Ph.D., CheckMate -9LA study investigator, Lung Clinic Grosshansdorf, German Center of Lung Research. “In the CheckMate -9LA trial, combining nivolumab and ipilimumab with two cycles of chemotherapy resulted in clinically meaningful overall survival benefits, which were consistent across patients with non-small cell lung cancer, regardless of PD-L1 expression levels or tumor histologies. Following today’s approval, clinicians in the EU will be able to offer patients a new option that may help achieve early disease control and improve survival.”

“The European Commission’s approval of Opdivo plus Yervoy with two cycles of chemotherapy is an important milestone for patients with metastatic non-small cell lung cancer who face a difficult prognosis despite recent advances,” said Abderrahim Oukessou, M.D., vice president, thoracic cancers development lead, Bristol Myers Squibb. “This innovative regimen is built on the only approved dual immunotherapy foundation. The combination of Opdivo plus Yervoy has previously demonstrated long-term survival outcomes across multiple cancer types, including melanoma and renal cell carcinoma. We look forward to collaborating with a broad range of European stakeholders to bring this unique combination of two potentially synergistic immunotherapies with chemotherapy to eligible patients with lung cancer.”

This decision marks the third indication for an Opdivo plus Yervoy-based regimen in the EU, following previous approvals in metastatic melanoma and advanced renal cell carcinoma (RCC). In addition to the EU, the combination of Opdivo plus Yervoy with two cycles of chemotherapy has been approved in 11 countries, including the U.S., for the first-line treatment of patients with metastatic NSCLC.

“Access to innovative medicines is key to improve outcomes for people impacted by lung cancer,” said Anne-Marie Baird, president of Lung Cancer Europe (LuCE). “We are pleased to see new treatment options approved that may potentially help more people with metastatic non-small cell lung cancer.''

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -9LA clinical trial.

CheckMate -9LA Efficacy and Safety Results

In the CheckMate -9LA trial, an interim analysis with a minimum follow-up of 8.1 months for OS demonstrated:

  • Opdivo plus Yervoy combined with two cycles of chemotherapy reduced the risk of death by 31% compared to chemotherapy alone [Hazard Ratio (HR): 0.69; 96.71% Confidence Interval (CI): 0.55 to 0.87; p=0.0006].
  • Median PFS with the combination was 6.8 months compared to 5.0 months with chemotherapy alone (HR: 0.70; 97.48% CI: 0.57 to 0.86; p=0.0001).
  • ORR was significantly higher for Opdivo plus Yervoy with two cycles of chemotherapy vs. chemotherapy alone: 38% vs. 25% (p=0.0003).

A subsequent analysis, with a minimum follow-up of 12.7 months, showed sustained improvements in OS compared to chemotherapy alone (HR: 0.66; 95% CI: 0.55 to 0.80).

The majority of select adverse reactions observed in patients who received Opdivo plus Yervoy with two cycles of chemotherapy were mild to moderate. Grade 3 or 4 treatment-related adverse events occurred in 47% of patients. The most frequent adverse reactions were fatigue (36%), nausea (26%), rash (25%), diarrhea (20%), pruritus (18%), decreased appetite (16%), hypothyroidism (15%) and vomiting (13%).

About CheckMate -9LA

CheckMate -9LA is an open-label, multi-center, randomized Phase 3 trial evaluating Opdivo (360 mg Q3W) plus Yervoy (1 mg/kg Q6W) combined with histology-based chemotherapy (two cycles) compared to chemotherapy alone (up to four cycles followed by optional pemetrexed maintenance therapy if eligible) as a first-line treatment in patients with metastatic non-small cell lung cancer (NSCLC) regardless of PD-L1 expression and histology. Patients in the experimental arm (n=361) were treated with dual immunotherapy for up to two years or until disease progression or unacceptable toxicity. Patients in the control arm (n=358) were treated with up to four cycles of chemotherapy and optional pemetrexed maintenance (if eligible) until disease progression or unacceptable toxicity.

The primary endpoint of the trial was overall survival (OS) in the intent-to-treat (ITT) population. Secondary hierarchical endpoints included progression-free survival (PFS) and overall response rate (ORR) as assessed by blinded independent review committee. Exploratory analyses from the study evaluated efficacy measures according to biomarkers.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer and accounts for up to 84% of diagnoses. Survival rates vary depending on the stage and type of the cancer when diagnosed. For patients diagnosed with metastatic NSCLC, the five-year survival rate is approximately 6%.

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients’ quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Opdivo

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 treated more than 35,000 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 65 countries, including the United States, the European Union, Japan and China. 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.

About Yervoy

Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.

U.S. FDA-APPROVED INDICATIONS

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC).

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY.

Checkmate Trials and Patient Populations

Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040–hepatocellular carcinoma, as a single agent or in combination with YERVOY

About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

SOURCE: Bristol Myers Squibb

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