FDA Approves Opdivo (nivolumab) + Yervoy (ipilimumab) for Patients with Hepatocellular Carcinoma (HCC) Previously Treated with Sorafenib
PRINCETON, N.J.--(BUSINESS WIRE) March 11, 2020 --Bristol Myers Squibb Company (NYSE: BMY) today announced that Opdivo (nivolumab) 1 mg/kg plus Yervoy (ipilimumab) 3 mg/kg (injections for intravenous use) was approved by the U.S. Food and Drug Administration (FDA) to treat hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib.1,2 Approval for this indication has been granted under accelerated approval based on overall response rate and duration of response seen in the Opdivo + Yervoy cohort of the Phase 1/2 CheckMate -040 trial.1,2,3 Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1,2
“HCC is an aggressive disease in need of different treatment approaches,”4,5,6 said Anthony B. El-Khoueiry, M.D., lead investigator and associate professor of clinical medicine and phase I program director at the Keck School of Medicine, University of Southern California (USC) and the USC Norris Comprehensive Cancer Center. “The overall response rate observed in the Opdivo + Yervoy cohort of the CheckMate -040 trial underscores the potential of this dual immunotherapy as a possible treatment option for patients.”1
In the CheckMate -040 cohort of HCC patients previously treated with sorafenib, after a minimum follow up of 28 months,1 33% (16/49; 95% CI: 20-48) of patients responded to treatment with Opdivo + Yervoy; 8% (4/49) had a complete response (CR) and 24% (12/49) had a partial response (PR).1 Duration of responses (DOR) ranged from 4.6 to 30.5+ months, with 88% lasting at least six months, 56% at least 12 months and 31% at least 24 months.1 Overall response rate (ORR) and DOR were assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).1 ORR assessed by BICR using modified RECIST was 35% (17/49; 95% CI: 22-50), with a CR reported in 12% (6/49) of patients and a PR reported in 22% (11/49) of patients.1
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, including Boxed WARNING for Yervoy (ipilimumab) regarding immune-mediated adverse reactions, as well as select safety information from CheckMate -040.
“The incidence of liver cancer is rising in the United States, and HCC is the most common and aggressive form of the disease,”4,5,6,7,8,9 said Andrea Wilson, president and founder, Blue Faery: The Adrienne Wilson Liver Cancer Association. “Today’s approval provides a new option for patients with HCC previously treated with sorafenib, giving the community more hope.”1
Opdivo + Yervoy is the only dual immunotherapy approved by the FDA in this setting. The therapy features a potentially synergistic mechanism of action that targets two different checkpoints (PD-1 and CTLA-4) and works in complementary ways.1
“We recognize there is a critical need to provide patients with aggressive forms of cancer, like HCC, new treatment options that may offer clinically meaningful and ultimately durable responses,” said Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb. “Today’s announcement builds on our legacy in pioneering immunotherapy treatments and is an important step in our commitment to transforming patients’ lives through science.”
Opdivo + Yervoy was granted Breakthrough Therapy Designation for this indication and a Priority Review from the FDA.
*Dr. Anthony B. El-Khoueiry is a paid consultant for Bristol Myers Squibb.
About the CheckMate -040 Trial Design
CheckMate -040 (NCT01658878) is a Phase 1/2 open-label study that included a cohort of patients with HCC who progressed on or were intolerant to sorafenib and received Opdivo + Yervoy.1,10 The trial included patients who were PD-L1 expressors and non-expressors.3 Key eligibility criteria included histologic confirmation of HCC and Child-Pugh Class A cirrhosis status.1 Additional eligibility criteria included those who were infected with active HCV or active HBV, or were uninfected.1,3 Patients with active autoimmune disease, brain metastasis, a history of hepatic encephalopathy, clinically significant ascites, infection with HIV, or active co-infection with HBV and HCV or HBV and HDV were excluded.1 Patients with known fibrolamellar HCC, sarcomatoid HCC, and mixed cholangiocarcinoma and HCC were also excluded.3 A total of 49 patients were treated with Opdivo 1 mg/kg IV and Yervoy 3 mg/kg IV every three weeks for four doses, followed by Opdivo 240 mg every two weeks until disease progression or unacceptable toxicity.1 The major efficacy outcome was ORR, as assessed by BICR using RECIST v1.1 and mRECIST.1 Duration of response was also assessed.1
Select Safety Profile from CheckMate -040 Study
The safety of Opdivo 1 mg/kg and Yervoy 3 mg/kg was evaluated in 49 patients.1 Serious adverse reactions occurred in 59% of patients receiving Opdivo + Yervoy.1 Treatment was discontinued in 29% of patients and delayed in 65% of patients for an adverse reaction.1 Serious adverse reactions reported in ≥4% of patients were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis.1 The most common adverse reactions (reported in ≥20% of patients) were rash (53%), pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough (37%), decreased appetite (35%), fatigue (27%), pyrexia (27%), abdominal pain (22%), headache (22%), nausea (20%), dizziness (20%), hypothyroidism (20%), and weight decreased (20%).1
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Bristol Myers Squibb: Advancing Oncology Research
At Bristol Myers Squibb, patients are at the center of everything we do. The focus of our research is to increase quality, long-term survival for patients and make cure a possibility. Through a unique multidisciplinary approach powered by translational science, we harness our deep scientific experience in oncology and Immuno-Oncology (I-O) research to identify novel treatments tailored to individual patient needs. Our researchers are developing a diverse, purposefully built pipeline designed to target different immune system pathways and address the complex and specific interactions between the tumor, its microenvironment and the immune system. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines, like I-O, 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, that continued approval of Opdivo in combination with Yervoy for the additional indication described in this release may be contingent upon verification and description of clinical benefit in confirmatory trials, that future study results will be consistent with the results to date, and whether Opdivo in combination with Yervoy for such additional indication described in this release will be commercially successful. 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.
- 1.OpdivoPrescribing Information. Opdivo U.S. Product Information. Last updated: March 2020. Princeton, NJ: Bristol Myers Squibb Company.
2.YervoyPrescribing Information. YervoyU.S. Product Information. Last updated: March 2020. Princeton, NJ: Bristol Myers Squibb Company.
3.Yau T, Kang YK, Kim TY, et al. Nivolumab + Ipilimumab Combination Therapy in Patients With Advanced Hepatocellular Carcinoma: Results From CheckMate 040. Presentation at American Society of Clinical Oncology congress, May 31-June 4, 2019.
4.Kumari R, Sahu MK, Tripathy A, et al. Hepatocellular Carcinoma Treatment: Hurdles, Advances and Prospects. Hepatic Oncology.2018;5(2):1-14.
5.Carusa S, Calatayud AL, Pilet J, et al. Analysis of Liver Cancer Cell Lines Identifies Agents With Likely Efficacy Against Hepatocellular Carcinoma and Markers of Response. Gastroenterology 2019;157:760–776.
6.Alqahtani A , Khan Z, Alloghbi A, et al. Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies. Medicina 2019; 9 (55):526.
7.Cronin KA , Lake AJ, Scott S, et al. Annual Report to the Nation on the Status of Cancer, Part I: National Cancer Statistics. Cancer.2018; 2785-2800.
8.SEER. Liver and Intrahepatic Bile Duct Cancer, CSR 1975-2016. https://seer.cancer.gov/archive/csr/1975_2015/results_merged/sect_14_liver_bile.pdf. Accessed February 25, 2020.
9.American Cancer Society. What is Liver Cancer? https://www.cancer.org/cancer/liver-cancer/about/what-is-liver-cancer.html. Accessed February 25, 2020.
10.ClinicalTrials.gov. An Immuno-therapy Study to Evaluate the Effectiveness, Safety and Tolerability of Nivolumab or Nivolumab in Combination With Other Agents in Patients With Advanced Liver Cancer (CheckMate040). https://clinicaltrials.gov/ct2/show/NCT01658878 . Published August 7, 2012. Updated January 21, 2020. Accessed February 25, 2020.
Source: Bristol Myers Squibb Company
Posted: March 2020
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- 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) 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
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