FDA Approves Opdivo (nivolumab) as Adjuvant Treatment of Completely Resected Esophageal or Gastroesophageal Junction Cancer in Patients who have Received Neoadjuvant Chemoradiotherapy

PRINCETON, N.J.–(BUSINESS WIRE) May 20, 2021 — Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has approved Opdivo® (nivolumab, injection for intravenous use) for the adjuvant treatment of completely resected esophageal or gastroesophageal junction (GEJ) cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT).¹ The approval is based on results from the Phase 3 CheckMate -577 trial that evaluated Opdivo (n=532) compared to placebo (n=262) in esophageal or GEJ cancer patients with residual pathologic disease following neoadjuvant CRT and complete resection.^1,2

In the trial, among patients who received Opdivo, median disease-free survival (DFS) was twice as long as in those who received placebo (22.4 months [95% Confidence Interval [CI]: 16.6 to 34.0] compared to 11.0 months [95% CI: 8.3 to 14.3]).1Opdivo reduced the risk of disease recurrence or death by 31% compared to placebo (Hazard Ratio [HR] 0.69; 95% CI: 0.56 to 0.85; P=0.0003).1 In an exploratory analysis, among patients with adenocarcinoma (n=563, 70.9%), mDFS was 19.4 months (95% CI: 15.9 to 29.4) with Opdivo versus 11.1 months (95% CI: 8.3 to 16.8) with placebo (unstratified HR 0.75; 95% CI: 0.59 to 0.96), and among squamous cell carcinoma patients (n=230, 29%), mDFS was 29.7 months (95% CI: 14.4 to NE) with Opdivo versus 11.0 months (95% CI: 7.6 to 17.8) with placebo (unstratified HR 0.61; 95% CI: 0.42 to 0.88).³

“Locally advanced esophageal and gastroesophageal junction cancers are aggressive tumor types that often require multiple approaches to address the disease, including chemotherapy, radiation and surgery,” said Ronan J. Kelly M.D., MBA., director, Baylor Scott & White Charles A. Sammons Cancer Center, and W.W. Caruth Jr. Endowed Chair of Immunology at Baylor University Medical Center.^3,4,5,6,7,8 “Even after neoadjuvant CRT followed by surgery, there may be a high risk of recurrence for patients who do not achieve a pathologic complete response.^2,3,7 In the CheckMate -577 trial, we saw a doubling in median disease-free survival compared to placebo, which suggests that Opdivo could become a new standard of care for these patients.^1,9 This is exciting news, providing renewed hope.”

Opdivo is associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); 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.1Please see the Important Safety Information section below, as well as select safety information from CheckMate -577.

“Esophageal and GEJ cancer patients with residual pathologic disease following neoadjuvant CRT and complete resection face a high risk of disease recurrence; however, the predominant option for these patients has been surveillance,” said Adam Lenkowsky, senior vice president and general manager, U.S. Cardiovascular, Immunology and Oncology, Bristol Myers Squibb.^3,7,9 “Today’s news marks an important step for patients as well as meaningful progress toward our commitment to pioneering immunotherapy treatment options in earlier stages of disease where there is the potential to reduce the risk of recurrence.”¹

This application was reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.10 The review was also conducted under the FDA’s Project Orbis initiative, which enabled concurrent review by the health authorities in Australia, Canada and Switzerland.

About CheckMate -577

CheckMate -577 was a Phase 3 randomized, placebo-controlled, double-blind, multi-center trial, evaluating Opdivo as an adjuvant treatment in patients with esophageal or GEJ cancer with residual pathologic disease following neoadjuvant CRT and complete resection.^1,2 The trial excluded patients who did not receive CRT prior to surgery, had stage IV resectable disease, autoimmune disease, or any condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications.¹ The primary endpoint of the trial was DFS (investigator assessed).¹ Following neoadjuvant CRT and complete tumor surgical resection (also known as trimodality therapy), a total of 794 patients were randomized to receive either Opdivo 240 mg (n=532) or placebo (n=262) by intravenous infusion every two weeks for 16 weeks, followed by Opdivo 480 mg or placebo by intravenous infusion every four weeks beginning at week 17.^1,2 Treatment was until disease recurrence, unacceptable toxicity, or for up to one year in total duration.¹

The FDA-approved dosing for Opdivo (injection for intravenous use) for adjuvant treatment of patients with resected esophageal or GEJ cancer is 240 mg intravenous infusion over 30 minutes every two weeks or 480 mg intravenous infusion over 30 minutes every four weeks until disease progression or unacceptable toxicity for a total treatment duration of one year.¹

Select Safety Profile from CheckMate -577 Study

Opdivo was discontinued in 12% of patients and was delayed in 28% of patients for an adverse reaction.¹ Serious adverse reactions occurred in 33% of patients receiving Opdivo.¹ A serious adverse reaction reported in ≥ 2% of patients who received Opdivo was pneumonitis.¹ A fatal adverse reaction of myocardial infarction occurred in one patient who received Opdivo.¹ The most common adverse reactions reported in ≥20% of patients treated with Opdivo were fatigue (34%), diarrhea (29%), nausea (23%), rash (21%), musculoskeletal pain (21%) and cough (20%).¹

About Esophageal and Gastroesophageal Junction Cancers

Esophageal and gastroesophageal junction cancers are classified as upper gastrointestinal cancers.¹¹

Esophageal cancer is a type of gastrointestinal cancer that starts in the inner layer of the esophagus (the mucosa) and grows.¹¹ In the United States, it is estimated there will be approximately 19,260 new cases of esophageal cancer diagnosed and 15,530 deaths resulted from the disease in 2021.¹² The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma.¹¹
The gastroesophageal junction (GEJ) is the area of the body that connects the lower part of the esophagus to the stomach.¹¹ The prevalence of GEJ cancer has continued to rise.^13,14

INDICATIONS

Opdivo (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT).

Opdivo (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

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 Bristol Myers Squibb 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, 2020, 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: May 2021. Princeton, NJ: Bristol-Myers Squibb Company.
   2.Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer following neoadjuvant chemoradiation therapy: first results of the CheckMate 577 study. Poster presented at: 2020 European Society for Medical Oncology (ESMO) Virtual Congress. September 19-21, 2020.
   3.Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021;384:1191-203.
   4.Kamarajah S, Navidi M, Wahed S, et al. Significance of Neoadjuvant Downstaging in Carcinoma of Esophagus and Gastroesophageal Junction. Ann Surg Oncol. 2020;27:3182-3192.
   5.Myint ZW and Goel G. Role of modern immunotherapy in gastrointestinal malignancies: a review of current clinical progress. J. Hematol. Oncol. (2017) 10:86,
   6.Shah AB, Sommerer KR, Almhanna K. Immune checkpoint inhibitors in gastrointestinal malignancies: what can we learn from experience with other tumors? Transl Gastroenterol Hepatol 2019;4:73.
   7.Murphy MB, Lianchum X, Patel VR, et al. Pathological Complete Response in Patients With Esophageal Cancer After the Trimodality Approach: The Association With Baseline Variables and Survival—The University of Texas MD Anderson Cancer Center Experience. Cancer 2017;123:4106-13.
   8.Saeed NA, Mellon EA, Meredith KL, et al. Adjuvant chemotherapy and outcomes in esophageal carcinoma. J Gastrointest Oncol 2017;8(5):816-824.
   9.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines: Esophageal and Esophagogastric Junction Cancers. https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf2021. Updated March 9, 2021. Accessed April 27, 2021.
   10.U.S. Food & Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program. Updated March 31, 2021. Accessed April 26, 2021.
   11.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 April 26, 2021.
   12.American Cancer Society. Key Statistics for Esophageal Cancer. https://www.cancer.org/cancer/esophagus-cancer/about/key-statistics.html. Updated January 12, 2021. Accessed April 26, 2021.
   13.Murphy AG, Lynch D and Kelly RJ. State of the art management of metastatic gastroesophageal cancer. Ann Transl Med. 2015;3(16):236.
   14.Bhurwal A, Brahmbatt B, Choudhry A, et al. Incidence of GE junction cancer continues to rise – analysis of SEER database. Gastrointestinal Endoscopy. 2019;89(6):AB362.https://doi.org/10.1016/j.gie.2019.03.522.

Source: Bristol Myers Squibb

Posted: May 2021

Related Articles:

• FDA Approves Opdivo (nivolumab) in Combination with Chemotherapy for Patients with Advanced or Metastatic Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma Regardless of PD-L1 Expression Status – April 16, 2021
• FDA Approves Opdivo (nivolumab) in Combination with Cabometyx (cabozantinib) as First-line Treatment for Patients with Advanced Renal Cell Carcinoma – January 22, 2021
• Bristol Myers Squibb Statement on Opdivo (nivolumab) Small Cell Lung Cancer U.S. Indication – December 29, 2020
• FDA Approves Opdivo (nivolumab) + Yervoy (ipilimumab) as the First and Only Immunotherapy Treatment for Previously Untreated Unresectable Malignant Pleural Mesothelioma – October 2, 2020
• FDA Approves Opdivo (nivolumab) for the Treatment of Patients with Advanced Esophageal Squamous Cell Carcinoma (ESCC) After Prior Fluoropyrimidine- and Platinum-based Chemotherapy – June 10, 2020
• FDA Approves Opdivo (nivolumab) + Yervoy (ipilimumab) Combined with Limited Chemotherapy as First-Line Treatment of Metastatic or Recurrent Non-Small Cell Lung Cancer – May 26, 2020
• FDA Approves Opdivo (nivolumab) + Yervoy (ipilimumab) as First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer Whose Tumors Express PD-L1≥1% – May 15, 2020
• FDA Approves Opdivo (nivolumab) + Yervoy (ipilimumab) for Patients with Hepatocellular Carcinoma (HCC) Previously Treated with Sorafenib – March 11, 2020
• FDA Approves Opdivo (nivolumab) for Certain Patients with Previously Treated Small Cell Lung Cancer – August 17, 2018
• Opdivo (nivolumab) + Low-Dose Yervoy (ipilimumab) Combination Approved for Previously Treated MSI-H/dMMR Metastatic Colorectal Cancer – July 11, 2018
• FDA Approves Opdivo (nivolumab) + Yervoy (ipilimumab) Combination as First-Line Treatment for Patients with Intermediate- and Poor-Risk Advanced Renal Cell Carcinoma – April 16, 2018
• Bristol-Myers Squibb’s Opdivo (nivolumab) Now the First and Only FDA-Approved PD-1 Inhibitor to Offer Every Four-Week Dosing – March 6, 2018
• Bristol-Myers Squibb Receives FDA Approval for Opdivo (nivolumab) as Adjuvant Therapy in Patients with Completely Resected Melanoma with Lymph Node Involvement or Metastatic Disease – December 20, 2017
• Bristol-Myers Squibb’s Opdivo (nivolumab) Receives FDA Approval for the Treatment of Hepatocellular Carcinoma Patients Previously Treated with Sorafenib – September 22, 2017
• Bristol-Myers Squibb Receives FDA Approval for Opdivo (nivolumab) in MSI-H or dMMR Metastatic Colorectal Cancer That Has Progressed Following Treatment – August 1, 2017
• Bristol-Myers Squibb Receives FDA Approval for Opdivo (nivolumab) in Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma – February 2, 2017
• Bristol-Myers Squibb’s Opdivo (nivolumab) is the First Immuno-Oncology Treatment to Receive FDA Approval Based on Overall Survival in Head and Neck Cancer – November 10, 2016
• Opdivo (nivolumab) FDA Approved for the Treatment of Hodgkin Lymphoma – May 17, 2016
• Bristol-Myers Squibb’s Opdivo (nivolumab) + Yervoy (ipilimumab) Regimen Receives Expanded FDA Approval in Unresectable or Metastatic Melanoma Across BRAF Status – January 23, 2016
• FDA Approves Opdivo to Treat Metastatic Renal Cell Carcinoma – November 23, 2015
• FDA Expands Approved Use of Opdivo (nivolumab) in Advanced Lung Cancer – October 9, 2015
• BMS Receives FDA Approval for Opdivo (nivolumab) + Yervoy (ipilimumab) Regimen in BRAF V600 Wild-Type Melanoma – October 1, 2015
• FDA Expands Approved use of Opdivo (nivolumab) to Treat Lung Cancer – March 4, 2015
• FDA Approves Opdivo (nivolumab) for Advanced Melanoma – December 22, 2014
• Opdivo (nivolumab) Demonstrates High Overall Response Rate of 87% for Treatment of Relapsed or Refractory Hodgkin Lymphoma – December 6, 2014
• Study Comparing Opdivo (nivolumab) to Chemotherapy Demonstrates Survival Benefit – November 16, 2014
• Phase 2 Objective Response Rate and Survival Data for Opdivo (nivolumab) in NSCLC to be Presented – October 30, 2014
• BMS Announces Collaboration to Evaluate Opdivo (nivolumab) in Combination to Treat Non-Small Cell Lung Cancer – October 6, 2014
• Bristol-Myers Squibb Announces Multiple Regulatory Milestones for Opdivo (nivolumab) – September 26, 2014

Opdivo (nivolumab) FDA Approval History