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FDA Approves Opdivo (nivolumab) for the Treatment of Patients with Advanced Esophageal Squamous Cell Carcinoma (ESCC) After Prior Fluoropyrimidine- and Platinum-based Chemotherapy

PRINCETON, N.J.--(BUSINESS WIRE) June 10, 2020 Bristol Myers Squibb (NYSE: BMY) today announced that Opdivo (nivolumab) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.1 This application was granted Priority Review Designation by the FDA, and the approval is based on the Phase 3 ATTRACTION-3 trial in which Opdivo (n=210) demonstrated superior overall survival (OS) versus taxane chemotherapy (n=209) (investigator’s choice of docetaxel or paclitaxel) (hazard ratio [HR] 0.77; 95% confidence interval [CI]: 0.62 to 0.96; p=0.0189).1,2 The median OS was 10.9 months (95% CI: 9.2 to 13.3) for Opdivo compared to 8.4 months (95% CI: 7.2 to 9.9) for docetaxel or paclitaxel.1 Opdivo is the first approved immunotherapy in this setting regardless of tumor PD-L1 expression level.

Opdivo is associated with the following Warnings and Precautions including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion-related reactions; embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.1 Please see the Important Safety Information section below.

“Many cases of esophageal cancer are diagnosed at the advanced stage, when the disease could have a significant impact on a patient’s health.3 Treatment options can be limited once patients with advanced esophageal squamous cell carcinoma progress,”2,4 said Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb. “The approval of Opdivo as a new treatment option for previously treated patients with advanced esophageal squamous cell carcinoma, regardless of PD-L1 expression, highlights our commitment to providing new options to address the unmet needs of patients and brings us another step closer to understanding the full potential of immunotherapy for gastrointestinal cancers.”1,2,5,6,7

About ATTRACTION-3

ATTRACTION-3 (NCT02569242) is a Phase 3, multicenter, randomized, active-controlled, open-label global study evaluating Opdivo versus taxane chemotherapy (investigator’s choice of docetaxel or paclitaxel) in patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma, refractory or intolerant to at least one prior fluoropyrimidine- and platinum-based regimen.1,2 The trial included patients regardless of tumor PD-L1 status, but tumor specimens were evaluated prospectively using the PD-L1 IHC 28-8 pharmDx assay at a central laboratory.1

The trial excluded patients who were refractory or intolerant to taxane therapy, had brain metastases that were symptomatic or required treatment, had autoimmune disease, used systemic corticosteroids or immunosuppressants or had apparent tumor invasion of organs adjacent to the esophageal tumor or had stents in the esophagus or respiratory tract.1 Patients were randomized to receive Opdivo 240 mg by intravenous infusion over 30 minutes every 2 weeks (n=210) or investigator’s choice of taxane chemotherapy (n=209) of either docetaxel 75 mg/m2 intravenously every 3 weeks (n=65), or paclitaxel 100 mg/m2 intravenously once a week for 6 weeks followed by 1 week off (n=144).1,2 Patient enrollment occurred predominantly in Asia, with the United States and Europe accounting for the remainder.2 Patients were treated until disease progression, assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or unacceptable toxicity.1

The major efficacy outcome measure was OS.1 Additional efficacy outcome measures included overall response rate (ORR) and progression-free survival (PFS) as assessed by the investigator using RECIST v1.1 and duration of response (DOR).1 There was no statistically significant difference between the two arms for ORR (19.3% [33/171, 95% CI: 13.7 to 26.0] versus 21.5% [34/158, 95% CI: 15.4 to 28.8] for Opdivo (0.6% complete response [CR] and 18.7% partial response [PR]) and investigator’s choice chemotherapy (1.3% CR and 20.3% PR), respectively; p=0.6323).1 The median PFS was 1.7 months (95% CI: 1.5 to 2.7) for Opdivo versus 3.4 months (95% CI: 3.0 to 4.2) for investigator’s choice chemotherapy (HR 1.1; 95% CI: 0.9 to 1.3), however it was not tested due to the pre-specified hierarchical testing strategy.1 This trial was sponsored by Ono Pharmaceutical Co. Ltd. of Japan, Bristol Myers Squibb’s development partner for Opdivo.8

Select Safety Profile from ATTRACTION-3

The safety of Opdivo was evaluated in ATTRACTION-3 in 209 patients.1 Serious adverse reactions occurred in 38% of patients receiving Opdivo.1 Serious adverse reactions reported in ≥2% of patients who received Opdivo were pneumonia, esophageal fistula, interstitial lung disease and pyrexia. The following fatal adverse reactions occurred in patients who received Opdivo: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).1 Opdivo was discontinued in 13% of patients and was delayed in 27% of patients for an adverse reaction.1 The most common adverse reactions occurring in ≥20% of Opdivo-treated patients were rash (22%) and decreased appetite (21%).1

About Esophageal Cancer

In the United States, it is estimated that approximately 18,440 new cases of esophageal cancer will be diagnosed and approximately 16,170 deaths will result from the disease this year alone.9 Esophageal cancer is a type of gastrointestinal cancer that starts in the inner layer of the esophagus (the mucosa) and grows.10 The mucosa is normally lined with squamous cells, and cancer starting in these cells is called squamous cell carcinoma, and accounts for less than 30% of esophageal cancers in the United States.10 For about 25% of patients, the disease is diagnosed in the advanced stage, which is typically harder to treat.3,7

Indication

OPDIVO® (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

The recommended dosage of OPDIVO for this indication is 240 mg IV infusion over 30 minutes every 2 weeks or 480 mg IV infusion over 30 minutes every 4 weeks, until disease progression or unacceptable toxicity.1

OPDIVO (10 mg/mL) is an injection for intravenous (IV) use.1

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 Bristol Myers Squibb’s Patient Access Support

Bristol Myers Squibb remains committed to providing assistance so that cancer patients who need our medicines can access them and expedite time to therapy.

BMS Access Support®, the Bristol Myers Squibb patient access and reimbursement program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance, as well as co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support can be obtained by calling BMS Access Support at 1-800-861-0048 or by visiting www.bmsaccesssupport.com.

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.

Cautionary Statement Regarding Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, whether Opdivo for the additional indication described in this release will be commercially successful and that continued approval of such product candidate for such additional indication described in this release may be contingent upon verification and description of clinical benefit in confirmatory trials. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2019, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

References

  1. 1.Opdivo Prescribing Information. Opdivo U.S. Product Information. Last updated: June 2020. Princeton, NJ: Bristol Myers Squibb Company.
    2. Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. The Lancet Oncology. 2019;20(11):1506–1517.
    3. American Cancer Society. Signs and Symptoms of Esophageal Cancer.  https://www.cancer.org/cancer/esophagus-cancer/detection-diagnosis-staging/signs-and-symptoms.html. Updated June 14, 2017. Accessed June 9, 2020.
    4. Huang J, Xu J, Chen Y, et al. Camrelizumab versus investigators choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. The Lancet Oncology. 2020;21(6):832–842.
    5. SEER. Esophageal Cancer, CSR1975-2016. https://seer.cancer.gov/csr/1975_2017/browse_csr.php?sectionSEL=8&pageSEL=sect_08_table.08 Accessed June 9, 2020.
    6. Siegel R, Miller K, Jemal A. Cancer Statistics, 2020. CA: A Cancer Journal for Clinicians. 2020;70(1):7–30
    7. Then E, Lopez M, Saleem S, et al. Esophageal Cancer: An Updated Surveillance Epidemiology and End Results Database Analysis. World Journal of Oncology. 2020;11(2):55–64.
    8. ClinicalTrials.gov. ONO-4538 Phase III Study A Multicenter, Randomized, Open-label Study in Patients With Unresectable Advanced or Recurrent Esophageal Cancer. https://clinicaltrials.gov/ct2/show/NCT02569242. Updated September 25, 2017. Accessed June 9, 2020
    9. American Cancer Society. Key Statistics for Esophageal Cancer.  https://www.cancer.org/cancer/esophagus-cancer/about/key-statistics.html.  Updated June 14, 2019. Accessed June 9, 2020. 
    10. American Cancer Society. What Is Cancer of the Esophagus?.  https://www.cancer.org/cancer/esophagus-cancer/about/what-is-cancer-of-the-esophagus.html. Updated March 20, 2020. Accessed June 9, 2020.

Source: Bristol Myers Squibb

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