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Opdivo® (nivolumab) in Combination with CABOMETYX® (cabozantinib) Demonstrates Significant Survival Benefits in Patients with Advanced Renal Cell Carcinoma in Pivotal Phase 3 CheckMate -9ER Trial

Opdivo in combination with CABOMETYX showed superior overall survival and doubled median progression-free survival and objective response rate with a favorable safety profile vs. sunitinib

Efficacy benefits were observed across key patient subgroups, including all International Metastatic Renal Cell Carcinoma Database Consortium risk and PD-L1 subgroups

Data selected for presentation during a Presidential Symposium and featured in official Press Programme at European Society for Medical Oncology Virtual Congress 2020

PRINCETON, N.J., & ALAMEDA, Calif.–(BUSINESS WIRE)–$BMY #BMSBristol Myers Squibb (NYSE: BMY) and Exelixis, Inc. (NASDAQ: EXEL) today announced the first presentation of results from the pivotal Phase 3 CheckMate -9ER trial, in which Opdivo®(nivolumab) in combination with CABOMETYX® (cabozantinib) demonstrated significant improvements across all efficacy endpoints, including overall survival (OS), in previously untreated advanced renal cell carcinoma (RCC). Opdivo in combination with CABOMETYX reduced the risk of death by 40% vs. sunitinib (Hazard Ratio [HR] 0.60; 98.89% Confidence Interval [CI]: 0.40 to 0.89; p=0.0010; median OS not reached in either arm). In patients receiving Opdivo in combination with CABOMETYX, median progression-free survival (PFS), the trial’s primary endpoint, was doubled compared to those receiving sunitinib alone: 16.6 months vs. 8.3 months, respectively (HR 0.51; 95% CI: 0.41 to 0.64; p<0.0001).

In addition, Opdivo in combination with CABOMETYX demonstrated a superior objective response rate (ORR), with twice as many patients responding compared to sunitinib (56% vs. 27%), and 8% vs. 5% achieved a complete response. Opdivo in combination with CABOMETYX was associated with a longer duration of response than sunitinib, with a median duration of 20.2 months vs. 11.5 months. All of these key efficacy results were consistent across the pre-specified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and PD-L1 subgroups.

Opdivo combined with CABOMETYX was well tolerated and reflected the known safety profiles of the immunotherapy and tyrosine kinase inhibitor (TKI) components in previously untreated advanced RCC. The incidence of treatment-related adverse events (TRAEs), including any-grade and high-grade TRAEs, was slightly higher for Opdivo in combination with CABOMETYX vs. sunitinib (97% vs. 93% for any-grade; 61% vs. 51% for grade 3 and higher), with a low rate of treatment-related discontinuations (6% for Opdivo only, 7% for CABOMETYX only and 3% for both Opdivo and CABOMETYX vs. 9% for sunitinib). Patients treated with Opdivo in combination with CABOMETYX reported significantly better health-related quality of life than those treated with sunitinib at most time points, according to National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) Kidney Symptom Index 19 (FKSI-19) scores.

These results (Presentation #696O_PR) will be featured as a Proffered Paper during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, on September 19, 2020 from 19:34-19:46 CEST.

“While we’ve seen considerable progress in the treatment of metastatic renal cell carcinoma, we must continue to research new options to help more patients achieve positive outcomes,” said Dr. Toni Choueiri, Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School. “The CheckMate -9ER data demonstrate meaningful efficacy benefits with nivolumab plus cabozantinib, which significantly improved overall survival and doubled progression-free survival and objective response rate with consistent effects observed across pre-specified subgroups. These results, along with a favorable tolerability profile and superior health-related quality of life, highlight this regimen’s potential importance among combinations of immunotherapies and tyrosine kinase inhibitors.”

Based on these efficacy and safety results from CheckMate -9ER, Bristol Myers Squibb and Exelixis’ partner Ipsen, which has exclusive rights to commercialize and develop CABOMETYX outside of the U.S. and Japan, each submitted type II variation applications for Opdivo plus CABOMETYX to the European Medicines Agency (EMA). On September 12, the EMA validated the type II variations, confirming the submissions are complete and beginning the EMA’s centralized review process. In addition, Bristol Myers Squibb and Exelixis recently completed their respective U.S. Food and Drug Administration (FDA) submissions for Opdivo in combination with CABOMETYX and, along with their partners, plan to discuss the CheckMate -9ER data with regulatory authorities across the world.

“These data are yet another example of the potential of immunotherapy-based combinations to meaningfully extend survival for patients with advanced cancers, strengthening our legacy in the genitourinary space,” said Nick Botwood, M.D., vice president, interim head, Oncology Development, Bristol Myers Squibb. “Opdivo was the first immune checkpoint inhibitor approved as a second-line treatment for advanced renal cell carcinoma, and then, with the addition of Yervoy, the first dual immunotherapy approved for certain patients in the first-line setting. With the promising results from CheckMate -9ER, we hope to bring the highly efficacious combination of Opdivo and CABOMETYX to patients with advanced renal cell carcinoma for whom an immunotherapy plus tyrosine kinase inhibitor regimen is chosen.”

“Considering the scientific and clinical evidence suggesting CABOMETYX uniquely creates a more immune-permissive tumor environment that may allow for synergistic antitumor activity when combined with Opdivo, we’re encouraged by the significant and consistent efficacy benefits shown in Checkmate -9ER for the first-line treatment of advanced kidney cancer, including all IMDC risk groups and PD-L1 status,” said Gisela Schwab, M.D., president, product development and medical affairs and chief medical officer, Exelixis. “The favorable efficacy and tolerability profile suggests that, if approved, CABOMETYX in combination with Opdivo would be an important new option for patients with advanced kidney cancer.”

Bristol Myers Squibb and Exelixis thank the patients and investigators who were 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 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, 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 140,000 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. Globally, the five-year survival rate for those diagnosed with metastatic, or advanced, kidney cancer is 12.1%.

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients’ quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

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.

About CABOMETYX®

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union, Japan and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

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) is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy. 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 advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

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) 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.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not be inclusive of 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 at any time after starting or discontinuing YERVOY. Early identification and management are essential to ensure safe use of 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 before each dose. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue YERVOY depending on severity. In general, if YERVOY requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less followed by corticosteroid taper for at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroid therapy. Institute hormone replacement therapy for endocrinopathies as warranted.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated pneumonitis occurred in 6% (25/407) of patients. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated pneumonitis occurred in 10% (5/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 4.4% (24/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 1.7% (2/119) of patients. In NSCLC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%) immune-mediated pneumonitis. Four patients (0.7%) died due to pneumonitis. The incidence and severity of immune-mediated pneumonitis in patients with NSCLC treated with OPDIVO 360 mg every 3 weeks in combination with YERVOY 1 mg/kg every 6 weeks and 2 cycles of platinum-doublet chemotherapy were comparable to treatment with OPDIVO in combination with YERVOY only.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated colitis occurred in 10% (5/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred in 10% (52/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred in 7% (8/119) of patients.

In a separate Phase 3 trial of YERVOY 3 mg/kg, immune-mediated diarrhea/colitis occurred in 12% (62/511) of patients, including Grade 3-5 (7%).

Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Addition of an alternative immunosuppressive agent to the corticosteroid therapy, or replacement of the corticosteroid therapy, should be considered in corticosteroid-refractory immune-mediated colitis if other causes are excluded.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. For patients without HCC, withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT is within normal limits at baseline and increases to >3 and up to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10 times the ULN. Permanently discontinue OPDIVO and administer corticosteroids if AST or ALT increases to >10 times the ULN or total bilirubin increases >3 times the ULN.

Contacts

Bristol Myers Squibb
Media Inquiries:
Media@BMS.com
609-252-3345

Investors:
Tim Power

609-252-7509

timothy.power@bms.com

Exelixis
Investors Contact:
Susan Hubbard

EVP, Public Affairs and Investor Relations

(650) 837-8194

shubbard@exelixis.com

Media Contact:
Lindsay Treadway

Senior Director, Public Affairs and Advocacy Relations

(650) 837-7522

ltreadway@exelixis.com

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