Opdivo demonstrates superior overall survival in this Phase 3 trial

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE:BMY) today announced that an open-label, randomized Phase 3 study evaluating Opdivo versus docetaxel in previously treated patients with advanced, squamous cell non-small cell lung cancer (NSCLC) was stopped early because an assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its endpoint, demonstrating superior overall survival in patients receiving Opdivo compared to the control arm. The company will share these data - which for the first time indicate a survival advantage with an anti-PD1 immune checkpoint inhibitor in lung cancer - with health authorities.

CheckMate -017 investigators are being informed of the decision to stop the comparative portion of the trial. Bristol-Myers Squibb is working to ensure that eligible patients will be informed of the opportunity to continue or start treatment with Opdivo in an open-label extension as part of the company's commitment to providing patient access to Opdivo, and characterizing long-term survival. The company will complete a full evaluation of the final CheckMate -017 data and work with investigators on the future presentation and publication of the results.

About the Study

CheckMate -017 is a Phase 3, open-label, randomized study of Opdivo versus docetaxel in previously treated patients with advanced or metastatic squamous cell NSCLC. The trial randomized 272 patients to receive either nivolumab 3 mg/kg intravenously every two weeks or docetaxel 75 mg/m2 intravenously every three weeks. The primary endpoint is overall survival. Secondary endpoints include objective response rate and progression free survival.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally, resulting in more than 1.5 million deaths each year according the World Health Organization. NSCLC is one of the most common types of the disease and accounts for approximately 85 percent of cases. Survival rates vary depending on the stage and type of the cancer when it is diagnosed. Globally, the five-year survival rate for Stage I NSCLC is between 47 and 50 percent; for Stage IV NSCLC, the five-year survival rate drops to two percent. Historically, the expected one-year survival rate for third-line squamous cell NSCLC patients is approximately 5.5% - 18%.

Immuno-Oncology at Bristol-Myers Squibb

Surgery, radiation, cytotoxic or targeted therapies have represented the mainstay of cancer treatment over the last several decades, but long-term survival and a positive quality of life have remained elusive for many patients with advanced disease.

To address this unmet medical need, Bristol-Myers Squibb is leading research in an innovative field of cancer research and treatment known as immuno-oncology, which involves agents whose primary mechanism is to work directly with the body's immune system to fight cancer. The company is exploring a variety of compounds and immunotherapeutic approaches for patients with different types of cancer, including researching the potential of combining immuno-oncology agents that target different and complementary pathways in the treatment of cancer.

Bristol-Myers Squibb is committed to advancing the science of immuno-oncology, with the goal of changing survival expectations and the way patients live with cancer.

About Opdivo

Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials - as monotherapy or in combination with other therapies - in which more than 7,000 patients have been enrolled worldwide.

In the U.S., Opdivo is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

IMPORTANT SAFETY INFORMATION

Immune-Mediated Pneumonitis

    --  Severe pneumonitis or interstitial lung disease, including fatal cases,
        occurred with OPDIVO treatment. Across the clinical trial experience in
        574 patients with solid tumors, fatal immune-mediated pneumonitis
        occurred in 0.9% (5/574) of patients receiving OPDIVO; no cases occurred
        in Trial 1. In Trial 1, pneumonitis, including interstitial lung
        disease, occurred in 3.4% (9/268) of patients receiving OPDIVO and none
        of the 102 patients receiving chemotherapy. Immune-mediated pneumonitis
        occurred in 2.2% (6/268) of patients receiving OPDIVO; one with Grade 3
        and five with Grade 2. Monitor patients for signs and symptoms of
        pneumonitis. Administer corticosteroids for Grade 2 or greater
        pneumonitis. Permanently discontinue OPDIVO for Grade 3 or 4 and
        withhold OPDIVO until resolution for Grade 2.

Immune-Mediated Colitis

    --  In Trial 1, diarrhea or colitis occurred in 21% (57/268) of patients
        receiving OPDIVO and 18% (18/102) of patients receiving chemotherapy.
        Immune-mediated colitis occurred in 2.2% (6/268) of patients receiving
        OPDIVO; five with Grade 3 and one with Grade 2. Monitor patients for
        immune-mediated colitis. Administer corticosteroids for Grade 2 (of more
        than 5 days duration), 3, or 4 colitis. Withhold OPDIVO for Grade 2 or
        3. Permanently discontinue OPDIVO for Grade 4 colitis or recurrent
        colitis upon restarting OPDIVO.

Immune-Mediated Hepatitis

    --  In Trial 1, there was an increased incidence of liver test abnormalities
        in the OPDIVO-treated group as compared to the chemotherapy-treated
        group, with increases in AST (28% vs 12%), alkaline phosphatase (22% vs
        13%), ALT (16% vs 5%), and total bilirubin (9% vs 0). Immune-mediated
        hepatitis occurred in 1.1% (3/268) of patients receiving OPDIVO; two
        with Grade 3 and one with Grade 2. Monitor patients for abnormal liver
        tests prior to and periodically during treatment. Administer
        corticosteroids for Grade 2 or greater transaminase elevations. Withhold
        OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4
        immune-mediated hepatitis.

Immune-Mediated Nephritis and Renal Dysfunction

    --  In Trial 1, there was an increased incidence of elevated creatinine in
        the OPDIVO-treated group as compared to the chemotherapy-treated group
        (13% vs 9%). Grade 2 or 3 immune-mediated nephritis or renal dysfunction
        occurred in 0.7% (2/268) of patients. Monitor patients for elevated
        serum creatinine prior to and periodically during treatment. For Grade 2
        or 3 serum creatinine elevation, withhold OPDIVO and administer
        corticosteroids; if worsening or no improvement occurs, permanently
        discontinue OPDIVO. Administer corticosteroids for Grade 4 serum
        creatinine elevation and permanently discontinue OPDIVO.

Immune-Mediated Hypothyroidism and Hyperthyroidism

    --  In Trial 1, Grade 1 or 2 hypothyroidism occurred in 8% (21/268) of
        patients receiving OPDIVO and none of the 102 patients receiving
        chemotherapy. Grade 1 or 2 hyperthyroidism occurred in 3% (8/268) of
        patients receiving OPDIVO and 1% (1/102) of patients receiving
        chemotherapy. Monitor thyroid function prior to and periodically during
        treatment. Administer hormone replacement therapy for hypothyroidism.
        Initiate medical management for control of hyperthyroidism.

Other Immune-Mediated Adverse Reactions

    --  In Trial 1, the following clinically significant, immune-mediated
        adverse reactions occurred in less than 1% of OPDIVO-treated patients:
        pancreatitis, uveitis, demyelination, autoimmune neuropathy, adrenal
        insufficiency, and facial and abducens nerve paresis. Across clinical
        trials of OPDIVO administered at doses 3 mg/kg and 10 mg/kg, additional
        clinically significant, immune-mediated adverse reactions were
        identified: hypophysitis, diabetic ketoacidosis, hypopituitarism,
        Guillian-Barré syndrome, and myasthenic syndrome. Based on the severity
        of adverse reaction, withhold OPDIVO, administer high-dose
        corticosteroids, and, if appropriate, initiate hormone-replacement
        therapy.

Embryofetal Toxicity

    --  Based on its mechanism of action, OPDIVO can cause fetal harm when
        administered to a pregnant woman. Advise pregnant women of the potential
        risk to a fetus. Advise females of reproductive potential to use
        effective contraception during treatment with OPDIVO and for at least 5
        months after the last dose of OPDIVO.

Lactation

    --  It is not known whether OPDIVO is present in human milk. Because many
        drugs, including antibodies, are excreted in human milk and because of
        the potential for serious adverse reactions in nursing infants from
        OPDIVO, advise women to discontinue breastfeeding during treatment.

Serious Adverse Reactions

    --  Serious adverse reactions occurred in 41% of patients receiving OPDIVO.
        Grade 3 and 4 adverse reactions occurred in 42% of patients receiving
        OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported
        in 2% to <5% of patients receiving OPDIVO were abdominal pain,
        hyponatremia, increased aspartate aminotransferase, and increased
        lipase.

Common Adverse Reactions

The most common adverse reaction (>=20%) reported with OPDIVO was rash (21%).

Please see US Full Prescribing Information for OPDIVO.

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, Bristol-Myers Squibb and Ono Pharmaceutical 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. Ono Pharmaceutical received manufacturing and marketing approval in Japan for Opdivo in July 2014 for the treatment of patients with unresectable melanoma, making Opdivo the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world.

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 www.bms.com, or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that Opdivo will receive regulatory approval for an additional indication in lung cancer or, if approved, that it will become commercially successful. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

    CONTACT: Bristol-Myers Squibb Company
             Media:
             Carrie Fernandez, 609-419-5448
             Cell: 215-859-2605
             carrie.fernandez@bms.com
             or
             Investors:
             Ranya Dajani, 609-252-5330
             ranya.dajani@bms.com
             or
             Ryan Asay, 609-252-5020
             ryan.asay@bms.com

    Source: Bristol-Myers Squibb Company