Bristol Myers Squibb Receives European Commission Approval for Opdivo (nivolumab) in Combination with Cabometyx (cabozantinib) as First-Line Treatment for Patients with Advanced Renal Cell Carcinoma

Approval based on Phase 3 CheckMate -9ER trial results showing Opdivo in combination with Cabometyx significantly improved overall survival and doubled median progression-free survival and objective response rates compared to sunitinib

Opdivo in combination with Cabometyx was generally well tolerated, with a low rate of treatment-related discontinuations

Two Opdivo-based therapies are now authorized for first-line treatment of patients with advanced renal cell carcinoma in the European Union: Opdivo plus Yervoy, a standard of care in intermediate- or poor-risk disease, and Opdivo in combination with Cabometyx, approved regardless of risk status

PRINCETON, NJ, USA I April 14, 2021 IBristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo® (nivolumab) in combination with Cabometyx® (cabozantinib) for the first-line treatment of adults with advanced renal cell carcinoma (RCC). The EC’s decision is based on results from the Phase 3 CheckMate -9ER trial, which demonstrated superior efficacy with Opdivo in combination with Cabometyx versus sunitinib across three key endpoints: progression-free survival (PFS), the primary endpoint, and objective response rate (ORR) and overall survival (OS). The combination of Opdivo and Cabometyx was well tolerated, with safety reflective of the known profiles of both medicines and a low rate of treatment-related adverse events (TRAEs) leading to discontinuation.

“With this approval, we can now offer patients two different Opdivo-based combinations that have demonstrated significant survival benefits versus sunitinib,” said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb. “Today’s milestone builds on our heritage of developing and delivering novel treatments for patients with advanced renal cell carcinoma, first with the only dual immunotherapy option, Opdivo plus Yervoy, and now with a new immunotherapy and tyrosine kinase inhibitor regimen. We look forward to working with a broad range of European stakeholders to bring Opdivo in combination with Cabometyx to patients who may benefit from this treatment.”

“The combination of nivolumab and cabozantinib pairs two proven agents for advanced renal cell carcinoma that together have shown superior efficacy across key endpoints and subgroups of patients compared to sunitinib in the CheckMate -9ER trial. Additionally, the combination’s safety profile was manageable with known protocols, leading to a low rate of treatment-related discontinuations,” said Marc-Oliver Grimm, M.D., professor of medicine and urology department head, Jena University Hospital. “With today’s approval, clinicians in the EU will be able to offer patients with advanced renal cell carcinoma an additional combination therapy that may help them achieve early control of their disease and improve survival outcomes.”

Opdivo in combination with Cabometyx was approved for RCC in the EU with a flexible dosing regimen, with the option to use either Opdivo 240 mg administered intravenously every two weeks or Opdivo 480 mg administered intravenously every four weeks in combination with Cabometyx 40 mg administered orally once daily.

In addition to the EU, Opdivo in combination with Cabometyx was approved for the first-line treatment of advanced RCC by the U.S. Food and Drug Administration in January 2021, and further applications are under review with health authorities globally. Results from the CheckMate -9ER trial were published in the New England Journal of Medicine in March 2021.

“With progress in research, patients are living longer with advanced kidney cancer than ever before, and so it has become increasingly important to consider how treatment impacts their daily lives,” said Rachel Giles, M.D., Ph.D., chair, International Kidney Cancer Coalition. “We are pleased to see the approval of a new, first-line combination for patients with advanced renal cell carcinoma that has the potential to not only control the disease but also maintain their health-related quality of life.”

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -9ER clinical trial.

CheckMate -9ER Efficacy and Safety Results

In the CheckMate -9ER trial, Opdivo in combination with Cabometyx showed superior PFS, ORR and OS versus sunitinib, with a low rate of TRAEs leading to discontinuation. With a minimum follow-up of 10.6 months:

  • PFS: Opdivo in combination with Cabometyx doubled median PFS (16.6 months vs. 8.3 months, respectively; HR 0.51; 95% CI: 0.41 to 0.64; p <0.0001), the trial’s primary endpoint, compared to sunitinib.
  • OS: The combination reduced the risk of death by 40% compared to sunitinib (HR: 0.60; 98.89% CI: 0.40 to 0.89; p=0.0010; median OS non-estimable for either arm).
  • ORR: Twice as many patients responded to Opdivo in combination with Cabometyx compared to sunitinib (55.7% vs. 27.1%).
  • Grade 3+ adverse events: Adverse reactions Grade 3 or higher in the trial were similar with Opdivo in combination with Cabometyx versus sunitinib (75% versus 71%).
  • TRAE discontinuations: Among patients treated with Opdivo and Cabometyx, 5.6% discontinued both agents due to TRAEs, 6.6% discontinued Opdivo only and 7.5% discontinued Cabometyx only. In the sunitinib arm, 8.8% of patients discontinued due to TRAEs.

An updated analysis conducted with 16.0 months minimum follow-up showed sustained efficacy improvements with Opdivo in combination with Cabometyx compared to sunitinib. These data were presented at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium.

With a minimum follow up of 16.0 months, the most frequent adverse reactions, occurring in 10% or more of patients, were diarrhea (64.7%), fatigue (51.3%), palmar-plantar erythrodysaesthesia syndrome (40.0%), stomatitis (38.8%), musculoskeletal pain (37.5%), hypertension (37.2%), rash (36.3%), hypothyroidism (35.6%), decreased appetite (30.3%), nausea (28.8%), abdominal pain (25.0%), dysgeusia (23.8%), upper respiratory tract infection (20.6%), cough (20.6%), pruritus (20.6%), arthralgia (19.4%), vomiting (18.4%), dysphonia (17.8%), headache (16.3%), dyspepsia (15.9%), dizziness (14.1%), constipation (14.1%), pyrexia (14.1%), edema (13.4%), muscle spasm (12.2%), dyspnea (11.6%), proteinuria (10.9%) and hyperthyroidism (10.0%).

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-L1≥1%) 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 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. The five-year survival rate for those diagnosed with metastatic, or advanced, kidney cancer is 13%.

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 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 October 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.

U.S. FDA-Approved Indications

OPDIVO® (nivolumab), as a single agent, 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 unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

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).

OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

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. This indication is approved under accelerated approval based on tumor 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), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients 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 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) 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.

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.

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 treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

Please see US Full Prescribing Information for OPDIVO and YERVOY.

Clinical Trials and Patient Populations

Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 025–previously treated renal cell carcinoma; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275–urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040–hepatocellular carcinoma, as a single agent or in combination with YERVOY; Checkmate 238–adjuvant treatment of melanoma; Attraction-3–esophageal squamous cell carcinoma

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.

SOURCE: Bristol Myers Squibb

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