Opdivo is the first and only immunotherapy approved in this patient population

In CheckMate -577, Opdivo doubled median disease-free survival versus placebo for these patients1

Approval expands the role of Opdivo in earlier stages of disease, with two indications in the adjuvant setting across three types of cancer1

PRINCETON, N.J.--(BUSINESS WIRE)-- 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]).1 Opdivo 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.1 Please 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.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO. Early identification and management are essential to ensure safe use of OPDIVO. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment with OPDIVO. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (