PRINCETON, N.J.–(BUSINESS WIRE) January 22, 2021– Bristol Myers Squibb (NYSE: BMY) today announced that Opdivo (nivolumab) 240 mg (injection for intravenous use) every two weeks or 480 mg every four weeks in combination with Cabometyx (cabozantinib) 40 mg once daily tablets was approved by the U.S. Food and Drug Administration (FDA) for the first-line treatment of patients with advanced renal cell carcinoma (RCC).¹ The approval is based on the Phase 3 CheckMate -9ER trial, which compared Opdivo in combination with Cabometyx (n=323) versus sunitinib (n=328) in patients with advanced RCC.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.⁴ Please see below for additional CheckMate -9ER data context.

“At Bristol Myers Squibb, we are focused on developing transformative medicines that may improve survival for people living with cancer. The role of Opdivo + Yervoy is well established for intermediate/poor-risk patients with advanced RCC, and today’s achievement extends the potential of an Opdivo-based combination to even more patients,” says Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb.¹ “Opdivo in combination with Cabometyx brings together the strong heritage of both medicines to now provide physicians a new combination in advanced RCC that may offer improved outcomes to patients for whom an immunotherapy plus tyrosine kinase inhibitor regimen is appropriate.”¹

Opdivo and Yervoy are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with 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

“This combination of cabozantinib and nivolumab significantly improved key efficacy measures compared to sunitinib – progression-free survival, overall survival and objective response rate – while showing a low rate of treatment discontinuations due to side effects. The therapeutic benefit demonstrated in CheckMate -9ER and quality of life measures explored emphasize the role of this combination for patients with advanced kidney cancer,” said Toni Choueiri, M.D., director, Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School.^1,2 “With this important FDA approval, the combination is poised to become a standard in newly diagnosed metastatic kidney cancer.”

In the CheckMate -9ER trial, the primary endpoint was progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR), and the secondary endpoints included overall survival (OS) and BICR-assessed objective response rate (ORR).¹ In the trial, patients treated with Opdivo in combination with Cabometyx lived twice as long without their tumors progressing as patients who were treated with sunitinib (median PFS was 16.6 months [95% Confidence Interval [CI]: 12.5-24.9] versus median PFS of 8.3 months [95% CI: 7.0-9.7]; [Hazard Ratio [HR]: 0.51 [95% CI: 0.41–0.64], P<0.0001; median follow-up of 18.1 months]; range: 10.6-30.6 months).^1,2 Opdivo in combination with Cabometyx also reduced the risk of death by 40% compared to sunitinib (HR: 0.60 [98.89% CI 0.40–0.89]; P=0.0010; median OS was not reached for Opdivo in combination with Cabometyx and not available for sunitinib [range: 22.6-NR months]).¹

Additionally, more patients responded to Opdivo in combination with Cabometyx than sunitinib, withan ORR of 55.7% (n=180/323) (95% CI: 50.1 to 61.2) versus 27.1% (n=89/328) (95% CI: 22.4 to 32.3); P<0.0001, respectively.¹ In the combination arm, 8.0% (n=26/323) of patients experienced a complete response and 47.7% (n=154/323) experienced a partial response versus 4.6% (n=15/328) and 22.6% (n=74/328) of those treated with sunitinib.^1,2 Among patients who responded, the median duration of response was 20.2 months for Opdivo in combination with Cabometyx (95% CI: 17.3 to NA) and 11.5 months for sunitinib (95% CI: 8.3 to 18.4).¹ Consistent results for PFS were observed across pre-specified subgroups of International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk categories and PD-L1 tumor expression status.¹

Adverse reactions greater than Grade 3 in the trial were similar with Opdivo in combination with Cabometyx versus sunitinib (75% versus 71%).² All-cause adverse reactions leading to discontinuation of either Opdivo or Cabometyx occurred in 19.7% of patients; 6.6% of Opdivo only, 7.5% of Cabometyx only and 5.6% of the combination due to same adverse reaction at the same time.^1,5

“While significant progress has been made in the treatment landscape for advanced kidney cancer over the last several years, patients still need more therapeutic options to treat this disease as we search for a possible cure,” said Bryan Lewis, president and co-founder of KidneyCAN.6,7 “As patients are living longer with advanced kidney cancer, focusing on the safety and effectiveness of new treatments has become even more important. The findings for the combination of Opdivo and Cabometyx in the CheckMate -9ER trial make the FDA approval of this combination a notable development for the patient community.”1

About CheckMate -9ER

CheckMate -9ER is an open-label, randomized, Phase 3 trial evaluating patients with previously untreated advanced renal cell carcinoma (RCC).1 A total of 651 patients (22% favorable risk, 58% intermediate risk, 20% poor risk) were randomized to Opdivo in combination with Cabometyx (n=323) versus sunitinib (n=328).1 Patients were randomized to receive 240 mg of Opdivo every two weeks intravenously and 40 mg of Cabometyx orally daily or sunitinib 50 mg orally daily for the first four weeks of a six-week cycle.1 Treatment with Opdivo continued until disease progression per Response Evaluation version 1.1 (RECIST v1.1) or unacceptable toxicity.1 The recommended dosing for Opdivo and Cabometyx is 240 mg of Opdivo every two weeks or 480 mg every four weeks in combination with 40 mg of Cabometyx once daily administered orally without food.¹ The recommended treatment for Opdivo is until disease progression, unacceptable toxicity or up to two years.1 Treatment with Cabometyx is until disease progression or unacceptable toxicity.¹ The primary endpoint was progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR), using RECIST v1.1.1 Secondary endpoints included overall survival (OS) and objective response rate (ORR), the latter of which was assessed by BICR using RECIST v1.1.1 The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

Select Safety Profile from CheckMate -9ER Study

Adverse reactions leading to discontinuation of either Opdivo or Cabometyx occurred in 19.7% of patients: 6.6% Opdivo only, 7.5% Cabometyx only and 5.6% both drugs due to the same adverse reaction at the same time.^1,5 Adverse reactions leading to dose interruption or reduction of either Opdivo or Cabometyx occurred in 83% of patients: 3% Opdivo only, 46% Cabometyx only, 21% both drugs due to same adverse reaction at the same time and 6% both drugs, sequentially.1 Serious adverse reactions occurred in 48% of patients receiving Opdivo in combination with Cabometyx (n=320).1 The most frequent (≥2%) serious adverse reactions in those patients were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection and hyponatremia.1 Fatal intestinal perforations occurred in 3 (0.9%) patients.1 The most common (≥20%) adverse reactions of any grade in patients receiving Opdivo and Cabometyx were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), cough (20%) and upper respiratory tract infection (20%).¹

About Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, accounting for approximately 15,000 deaths in the United States each year.8,9 RCC is approximately twice as common in men as in women.¹⁰ In the United States, the five-year survival rate, based on data from 2010 to 2016, for those diagnosed with metastatic (or advanced) kidney and renal pelvis cancer is 13%.⁹

INDICATIONS

Opdivo® (nivolumab), in combination with Yervoy® (ipilimumab), is indicated for the first-line treatment of patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

Opdivo® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

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

Bristol Myers Squibb is inspired by a single vision — transforming people’s 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 in combination with Cabometyx for the indication described in this release will be commercially successful and that continued approval of such combination treatment for such 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

Source: Bristol Myers Squibb

Posted: January 2021

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Opdivo (nivolumab) FDA Approval History

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