Opdivo in combination with CABOMETYX reduced the risk of death by 23% in the first-line treatment of advanced renal cell carcinoma vs. sunitinib

Four-year results demonstrating continued benefits with immunotherapy-tyrosine kinase inhibitor combination to be shared in an oral presentation at ASCO GU 2024

PRINCETON, N.J. & ALAMEDA, Calif.--(BUSINESS WIRE)-- 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 Opdivo plus CABOMETYX over 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 Médicas y Nutrición Salvador Zubirán, 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-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 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.

INDICATIONS

OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years of age and older with unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years of age and older with unresectable or metastatic melanoma.

OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.

OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).

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 adult 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 adult 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 adult patients with advanced renal cell carcinoma (RCC).

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

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), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult 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 treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).

OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune- mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune- mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (