PRINCETON - Bristol Myers Squibb (NYSE: BMY) and Exelixis, Inc. (NASDAQ: EXEL) today announced four-year follow-up results from the CheckMate -9ER trial evaluating Opdivo (nivolumab) in combination with CABOMETYX (cabozantinib) vs. sunitinib in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC).
Results continued to show superior progression-free survival (PFS) and objective response rates (ORR) in patients treated with Opdivoplus CABOMETYXover sunitinib, regardless of risk classification based on International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scores. Superior overall survival (OS) was also observed in patients treated with the combination. These updated results, including data showing health-related quality-of-life benefits with Opdivo in combination with CABOMETYX vs. sunitinib, will be featured in an oral presentation (Abstract #362) at the American Society of Clinical Oncology (ASCO) 2024 Genitourinary Cancers Symposium from January 25-27, 2024.
'Renal cell carcinoma can be very challenging to treat and patients who are diagnosed with advanced disease or develop metastasis often face poor outcomes,' said Maria Teresa Bourlon, Urologic Oncology Clinic, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico. 'These updated results from the CheckMate -9ER trial continue to support the role of nivolumab in combination with cabozantinib as an important first-line treatment option for this devastating disease, demonstrating durable efficacy across its multiple study endpoints, including a 23% reduction in the risk of death.'
At a median follow-up of 55.6 months (48.1 months minimum), all patients randomized to the Opdivo plus CABOMETYX treatment arm (n=323) continued to experience benefits over those who received sunitinib (n=328) across efficacy endpoints
PFS (primary endpoint): PFS continued to favor Opdivo plus CABOMETYX, with median PFS nearly doubled with the combination regimen at 16.4 months vs. 8.4 months with sunitinib (Hazard Ratio [HR] 0.58; 95% Confidence Interval [CI]: 0.49 to 0.70).
OS (secondary endpoint): Treatment with Opdivo in combination with CABOMETYX elicited durable survival benefit over sunitinib, with a median OS of 46.5 months compared to 36.0 months with sunitinib (HR 0.77; 95% CI: 0.63 to 0.95).
ORR (secondary endpoint): The combination regimen showed durable response improvements, doubling the ORR compared to sunitinib (55.7% vs. 27.7%, respectively).
Complete response (CR): Patients who received Opdivo plus CABOMETYX continued to show CR benefit, with triple the number of patients achieving CR vs. sunitinib (13.6% vs. 4.6%).
Duration of response (DOR): Opdivo plus CABOMETYX was associated with a longer median DOR of 22.0 months vs. 15.2 months in the sunitinib group.
Safety: No new safety concerns were identified in this follow-up analysis. Among all treated patients, any-grade treatment-related adverse events (TRAEs) occurred in 97.5% in the Opdivo plus CABOMETYX group compared to 93.1% in the sunitinib group. Grade 3 TRAEs occurred in 67.5% of Opdivo plus CABOMETYX-treated patients vs. 55.3% in sunitinib-treated patients.
Additionally, in exploratory analyses, durable and clinically meaningful benefits were observed in patient subgroups across risk groups, including within the favorable-risk and intermediate- and poor-risk groups: OS: Among patients with intermediate-/poor-risk, median OS was 43.9 months for those treated with Opdivo plus CABOMETYX vs. 29.3 months with sunitinib (HR 0.73; 95% CI: 0.58 to 0.91). In patients with favorable risk, median OS was similar across treatment arms at 52.9 months with the combination regimen and 58.9 months with sunitinib (HR 1.10; 95% CI: 0.69 to 1.75).
PFS: PFS was improved with the combination regimen in patients with intermediate-/poor-risk with a median PFS of 15.4 months compared to 7.1 months with sunitinib (HR 0.56; 95% CI: 0.45 to 0.68), as well as in those with favorable risk at 21.4 months vs. 12.8 months (HR 0.69; 95% CI: 0.48 to 1.00).
ORR: In patients with intermediate-/ poor-risk, ORR was more than doubled at 52.6% with Opdivo and CABOMETYX vs. 23.0% with sunitinib. In those with favorable risk, ORR was 66.2% vs. 44.4%, respectively.
CR: Among those with intermediate-/poor-risk profiles, the number of patients who achieved CR more than tripled (12.9% vs. 3.5%) with the combination regimen compared to sunitinib. In those with favorable risk profiles, the number of patients who achieved CR was doubled (16.2% vs. 8.3%) with the combination regimen.
DOR: Median DOR was also improved with Opdivo and CABOMETYX across both groups. Among the intermediate- and poor-risk group, those treated with the combination regimen had a median DOR of 23.1 months vs. 13.8 months with sunitinib. Among the favorable risk group, median DOR was 18.7 months vs. 17.8 months, respectively.
'There has been an ongoing need for therapeutic options that can provide patients with previously untreated advanced or metastatic renal cell carcinoma with the potential for disease control and extended survival. By combining the power of these two unique modalities, we established a new standard of care with Opdivo and CABOMETYX, building on our commitment to improving outcomes for patients with advanced cancers, including but not limited to genitourinary cancers,' said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. 'Now, after more than four years of follow up, the data continue to underscore the value of Opdivo-based combinations in the GU cancer treatment paradigm with the potential to help patients diagnosed with advanced RCC live longer, regardless of risk classification.'
'These results from CheckMate -9ER provide hope that patients with previously untreated advanced kidney cancer may experience a long-term survival benefit. We are pleased to see that the combination of CABOMETYX and Opdivo continues to demonstrate durable and clinically meaningful efficacy after four years of follow-up in this patient population across risk groups, reinforcing the value of this regimen as a standard of care in this setting,' said Amy Peterson, M.D., executive vice president, product development & medical affairs, and chief medical officer, Exelixis. 'It is also encouraging that CABOMETYX in combination with Opdivo demonstrated superior PFS and OS benefits in patients who had disease burdens in often challenging-to-treat areas, including bone, liver and lung metastases. The totality of these encouraging findings, achieved in partnership with Bristol Myers Squibb, underscore our commitment to collaborating with the scientific community to advance treatment regimens for patients with advanced cancers.'
Bristol Myers Squibb and Exelixis thank the patients and investigators involved in the CheckMate -9ER clinical trial.
About CheckMate -9ER
CheckMate -9ER is an open-label, randomized, multi-national Phase 3 trial evaluating patients with previously untreated advanced or metastatic renal cell carcinoma (RCC). A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L11%) were randomized to receive Opdivo plus CABOMETYX (n=323) vs. sunitinib (n=328). The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis is comparing the doublet combination vs. sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co. and co-funded by Exelixis, Inc., Ipsen Pharma SAS and Takeda Pharmaceutical Company Limited.
About Renal Cell Carcinoma
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, accounting for more than 431,000 new cases and 179,000 deaths worldwide each year. RCC is approximately twice as common in men as in women, with the highest rates of the disease in North America and Europe. At diagnosis, up to 30% of patients present with advanced or metastatic RCC.
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 understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach 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. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response. By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo's leading global development program is based on Bristol Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In September 2015, the Company's Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
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.
About Exelixis
Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future.
Bristol Myers Squibb 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 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 future study results may not be consistent with the results to date, that Opdivo (nivolumab) in combination with CABOMETYX (cabozantinib) for the indication described in this release will be commercially successful, that any marketing approvals, if granted, may have significant limitations on their use, 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 additional 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, 2022, 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.
Exelixis Forward-Looking Statements
This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of updated results from the CheckMate -9ER trial at ASCO GU 2024; the therapeutic potential of cabozantinib in combination with nivolumab and Exelixis' belief that the regimen may provide a long-term survival benefit for patients with previously untreated advanced kidney cancer, regardless of risk classification; Exelixis' commitment to collaborating with the scientific community to advance treatment regimens for patients with advanced cancers and Exelixis' scientific pursuit to create transformational treatments that give more patients hope for the future. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the referenced times; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis' and Bristol Myers Squibb's continuing compliance with applicable legal and regulatory requirements; the potential failure of cabozantinib in combination with nivolumab to demonstrate safety and/or efficacy in future clinical testing; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib; the costs of conducting clinical trials; Exelixis' dependence on third-party vendors for the development, manufacture and supply of cabozantinib; Exelixis' and Bristol Myers Squibb's ability to protect their respective intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions and other factors affecting Exelixis and its development programs detailed from time to time under the caption 'Risk Factors' in Exelixis' most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis' future filings with the Securities and Exchange Commission. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.
Contact:
Susan Hubbard
Tel: (650) 837-8194
Email: shubbard@exelixis.com
BRISTOL-MYERS SQUIBB COMPANY 
