Data to be featured at ASCO GU 2023 demonstrate continued overall survival, progression-free survival and objective response rate benefits with Opdivo in combination with CABOMETYX compared to sunitinib, regardless of IMDC risk score
These three-year data – with a median follow-up of 44 months – from CheckMate -9ER represent the longest reported follow-up in any Phase 3 trial with an immunotherapy-tyrosine kinase inhibitor regimen in this population
In an exploratory biomarker analysis, median progression-free survival and overall survival were improved with the combination of Opdivo and CABOMETYX regardless of PD-L1 status
PRINCETON, NJ & ALAMEDA, CA, USA I February 13, 2023 IBristol Myers Squibb (NYSE: BMY) and Exelixis, Inc. (NASDAQ: EXEL) today announced three-year (36.5 months minimum; 44.0 months median) follow-up results from the Phase 3 CheckMate -9ER trial, demonstrating sustained survival and response rate benefits with the combination of Opdivo® (nivolumab) and CABOMETYX® (cabozantinib) versus sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC). Additionally, a biomarker analysis showed that improvements in median progression-free survival (PFS) and overall survival (OS) were sustained with the combination of Opdivo and CABOMETYX regardless of PD-L1 status. These updated results will be featured in one oral and one poster presentation at the American Society of Clinical Oncology (ASCO) 2023 Genitourinary Cancers Symposium from February 16-18, 2023.
“Despite the progress made through science and medicine, there remains a need for treatment options that can durably extend survival for patients with metastatic renal cell carcinoma, especially for those classified as higher risk,” said Mauricio Burotto, M.D., medical director, Bradford Hill Clinical Research Center, Santiago, Chile. “With these updated results from CheckMate -9ER, we’ve now seen nivolumab in combination with cabozantinib durably extend survival and sustain response benefits compared to sunitinib for over three years, regardless of patients’ risk classification. These results reinforce the importance of this immunotherapy-tyrosine kinase inhibitor regimen for patients and its potential to help change survival expectations for patients with this challenging cancer.”
Abstract #603: Nivolumab plus cabozantinib vs sunitinib for first-line treatment of advanced renal cell carcinoma (aRCC): 3-year follow-up from the phase 3 CheckMate -9ER trial (Burotto, et. al.)
With a median follow-up of 44.0 months (36.5 months minimum), Opdivo in combination with CABOMETYX (n=323) continued to show superior OS, PFS, objective response rate (ORR), duration of response (DoR) and complete response (CR) rates versus sunitinib (n=328). No new safety signals were seen with extended follow-up. Within the full study population:
- OS: Treatment with Opdivo in combination with CABOMETYX continued to show a 30% reduction in the risk of death (Hazard Ratio [HR] 0.70; 95% Confidence Interval [CI]: 0.56 to 0.87), and improvement in median OS vs. sunitinib (49.5 months vs. 35.5 months, respectively). Additionally, median OS improved by 11.8 months since the previous data cut at 32.9 months median follow-up.
- PFS: PFS benefits were sustained, with the combination continuing to double median PFS vs. sunitinib (16.6 months vs. 8.4 months, respectively; HR 0.58; 95% CI: 0.48 to 0.71).
- ORR and DoR: ORR benefits were maintained, with nearly twice as many patients responding to Opdivo in combination with CABOMETYX vs. sunitinib (55.7% vs. 28.4%). Responses also continued to be more durable with the combination, with a median DoR of 23.1 months compared to 15.2 months with sunitinib.
- CR: CR rates were also sustained, with 12.4% of those treated with Opdivo in combination with CABOMETYX having a CR vs. 5.2% of those treated with sunitinib.
- Safety: 97% of patients treated with Opdivo in combination with CABOMETYX experienced a treatment-related adverse event (TRAE) of any grade compared to 93% of patients treated with sunitinib; 67% vs. 55% had a grade ≥3 TRAE, respectively.
Results were also assessed by the following International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores: favorable, intermediate, intermediate/poor and poor. Benefits were seen with Opdivo in combination with CABOMETYX across all efficacy measures (OS, PFS, ORR and CR), regardless of IMDC risk.
Abstract #608: Biomarker analysis from the phase 3 CheckMate 9ER trial of nivolumab + cabozantinib v sunitinib for advanced renal cell carcinoma (aRCC) (Choueiri, et. al.)
In an exploratory post-hoc analysis from CheckMate -9ER with 44.0 months median follow-up, improvements were observed in both median PFS and OS with Opdivo in combination with CABOMETYX regardless of PD-L1 status. PFS and OS were evaluated by tumor PD-L1 expression (<1% or ≥1%), CD8% (low, medium, high by tertiles), and CD8 topology phenotype (cold, excluded, inflamed), and assessed for association using Kaplan-Meier (KM) methods with log-rank test (PD-L1 and CD8), and Cox proportional hazard (Cox PH) models (CD8). Biomarkers previously found to be predictive of anti-PD-L1 + anti-VEGF outcomes, including established gene expression signatures, were not necessarily predictive of efficacy with anti-PD-1 + anti-VEGF targeted therapy, suggesting that key determinants of response to anti-PD-1 vs. anti-PD-L1 therapies may differ.
“We have a strong heritage of bringing immunotherapy-based combinations to patients with advanced renal cell carcinoma and transforming patient outcomes with Opdivo-based combinations across several cancer types,” said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb. “The updated data from CheckMate -9ER further reinforce the use of Opdivo in combination with CABOMETYX for the first-line treatment of patients with advanced renal cell carcinoma. We remain committed to collaboration across the scientific community and our ongoing exploration of combination approaches with our proven cancer agents in the pursuit of solutions that may help improve long-term outcomes for as many patients as possible.”
“With forty-four months median follow-up, the compelling survival benefit further reinforces the value of the CABOMETYX and Opdivo combination regimen as a first-line option for patients with advanced kidney cancer,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “We are pleased to share these long-term findings at ASCO GU and remain steadfast in our longstanding commitment to improving outcomes for patients living with advanced kidney cancer.”
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 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 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.
OPDIVO INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic melanoma.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.
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.
Please see accompanying full Prescribing Information https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf
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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.
About Exelixis
Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by bi-coastal centers of 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. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com, follow @ExelixisInc on Twitter, like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn.
SOURCE: Bristol Myers Squibb
