U.S. Food and Drug Administration Approves Opdivo (nivolumab) for the Adjuvant Treatment of Patients with High-Risk Urothelial Carcinoma

PRINCETON, N.J.–(BUSINESS WIRE) August 20, 2021 — Bristol Myers Squibb (NYSE: BMY) today announced that Opdivo (nivolumab) 240 mg every two weeks or 480 mg every four weeks (injection for intravenous use) was approved by the U.S. Food and Drug Administration (FDA) for the adjuvant treatment of patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection, regardless of prior neoadjuvant chemotherapy, nodal involvement or PD-L1 status.1 The approval is based on the Phase 3 CheckMate -274 trial, which compared Opdivo 240 mg (n=353) to placebo (n=356).1 This application was approved 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.²

In the trial, among patients who received Opdivo, median disease-free survival (DFS) was nearly twice as long as in those who received placebo (20.8 months [95% Confidence Interval (CI): 16.5 to 27.6] versus 10.8 months [95% CI: 8.3 to 13.9]).¹Opdivo reduced the risk of disease recurrence or death by 30% compared to placebo (Hazard Ratio [HR] 0.70, 95% CI: 0.57 to 0.86; P=0.0008).¹ Among patients whose tumors express PD-L1 ≥1%, median DFS was not reached (95% CI: 21.2 to NE; n=140) for those who received Opdivo versus 8.4 months (95% CI: 5.6 to 21.2; n=142) for placebo; Opdivo reduced the risk of disease recurrence or death by 45% (HR 0.55, 95% CI: 0.39 to 0.77; P=0.0005).¹

“This approval is a major milestone for patients who have undergone major surgery to remove the bladder or parts of the urinary tract and are in need of additional treatment approaches that can help reduce the risk of their UC returning,” said Matthew D. Galsky,* M.D., a CheckMate -274 primary investigator and Professor of Medicine, Director of Genitourinary Medical Oncology, Co-Director of the Center of Excellence for Bladder Cancer, and Associate Director for Translational Research at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai.³ “Nivolumabprovides a new FDA-approved treatment shown to reduce the risk of disease recurrence or death based on the safety and efficacy findings from CheckMate -274, and has the potential to become a new standard of care option in this setting.”¹

Opdivo is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, 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 Important Safety Information below.

“At Bristol Myers Squibb, our leading research in immunotherapy has helped transform the way many cancers are treated, and we are continuing to bring these advancements to patients with earlier stages of disease, particularly in challenging cancers with significant unmet need,” said Adam Lenkowsky, senior vice president and general manager, U.S. Cardiovascular, Immunology and Oncology, Bristol Myers Squibb. “UC is the third type of cancer where Opdivo has been the first approved PD-1 inhibitor in the adjuvant setting. Now with this advancement, we can offer new hope to the conversations between healthcare providers and their UC patients where historically no approved treatment options have existed to help prevent disease recurrence post-surgery.”1

The results from the CheckMate -274 trial are confirmatory evidence for Opdivo’s accelerated approval for patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy received in February 2017. These results support conversion of Opdivo’s accelerated approval to a regular approval in this setting.

About CheckMate -274

CheckMate -274 is a randomized, double-blind, placebo-controlled, multi-center trial evaluating Opdivo as an adjuvant treatment in patients who had undergone radical resection of urothelial carcinoma (UC) originating in the bladder or upper urinary tract and were at high risk of recurrence.¹ The UC pathologic staging criteria that defines high risk patients was ypT2-ypT4a or ypN+ for patients who received neoadjuvant cisplatin chemotherapy or pT3-pT4a or pN+ for patients who did not receive neoadjuvant cisplatin and who also either were ineligible for or refused adjuvant cisplatin chemotherapy.¹

Patients were randomized (n=353 and n=356 to the Opdivo and placebo arms, respectively) to receive Opdivo 240 mg or placebo by intravenous infusion over 30 minutes every two weeks until recurrence or unacceptable toxicity for a maximum treatment duration of one year.1 Eligible patients were randomized in a 1:1 ratio to Opdivo or placebo and were stratified by pathologic nodal status (N+ vs. N0/x with <10 nodes removed vs. N0 with ≥10 nodes removed), tumor cells expressing PD-L1 (≥1% vs. <1%/indeterminate as determined by the central lab using the PD L1 IHC 28-8 pharmDx assay), and use of neoadjuvant cisplatin (yes vs. no).1 The major efficacy outcome measures were investigator-assessed DFS in all randomized patients and in patients with tumors expressing PD-L1 ≥1%.1 DFS was defined as time to first recurrence (local urothelial tract, local non-urothelial tract, or distant metastasis), or death.1 Additional efficacy outcome measures included overall survival.1 The FDA-approved dosing for Opdivo is 240 mg every two weeks (30-minute intravenous infusion) or 480 mg every four weeks (30-minute intravenous infusion) until disease recurrence or unacceptable toxicity for up to one year.¹

Select Safety Profile from CheckMate -274 Study

Adverse reactions leading to discontinuation of Opdivo occurred in 18% of patients.1Opdivo was delayed for adverse reaction in 33% of patients.1 Serious adverse reactions occurred in 30% of patients receiving Opdivo.1 The most frequent (≥2%) serious adverse reaction in patients receiving Opdivo was urinary tract infection.¹ Fatal adverse reactions occurred in 1% of patients and included pneumonitis (0.6%).¹ The most common (≥20%) adverse reactions were rash (36%), fatigue (36%), diarrhea (30%), pruritus (30%), musculoskeletal pain (28%), and urinary tract infection (22%).¹

About Urothelial Carcinoma

Urothelial carcinoma (UC), which most frequently begins in the cells that line the inside of the bladder, is the most common type of bladder cancer in adults in the United States.⁴ Each year, 81,000 new cases of bladder cancer are diagnosed and a majority of those cases are UC.^4,5 In addition to the bladder, UC can occur in other parts of the urinary tract, including the ureter and renal pelvis.4 Although UC can be diagnosed early, the rates of recurrence and disease progression can be high.^6,7 The survival rate can vary depending on the stage and other factors when diagnosed; for patients with metastatic UC, the prognosis is often poor.^5,8

INDICATIONS

OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.

OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

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.

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).

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 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 Supportat 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.

*Dr. Matthew D. Galsky has been a paid consultant to Bristol Myers Squibb.

References

Source: Bristol Myers Squibb

Posted: August 2021

FDA Approves Opdivo (nivolumab) as Adjuvant Treatment of Completely Resected Esophageal or Gastroesophageal Junction Cancer in Patients who have Received Neoadjuvant Chemoradiotherapy – May 20, 2021
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

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