Bristol Myers Squibb Submits Prospectus for First I-O/I-O Combination Therapy Approved in Europe for Previously Untreated Advanced Renal Cell Carcinoma

January 15, 2019 /PRNewswire/ -- On January 14, Bristol-Myers Squibb (NYSE: BMY) announced that the European Commission has approved the regimen of nivolumab (Opdivo) at 3 mg/kg in combination with ipilimumab at 1 mg/kg (“low dose”) for the first-line treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC). This is the first immuno-oncology (I-O) combination therapy approved in the EU for this patient population.

“Currently, fewer than 50% of patients with metastatic renal cell carcinoma (mRCC) survive beyond two years, and complete responses are rarely observed. These realities underscore the urgent need for new therapies for renal cell carcinoma,” stated Dr. Bernard Escudier, Former Chair of the Genitourinary Oncology Committee at Gustave Roussy Cancer Institute in France. “This approval provides a new first-line treatment option for patients in the European Union. Compared with sunitinib, this immuno-oncology (I-O) combination regimen demonstrates a complete response rate of nearly 10%, a significantly improved overall survival (OS), and a lower incidence of grade 3 and 4 adverse events.”

This approval is based on the results of the Phase III CheckMate-214 clinical study. The trial was terminated early following a pre-planned interim analysis. The analysis demonstrated that combination therapy with nivolumab and low-dose ipilimumab significantly improved overall survival (OS). Compared with the current standard of care, sunitinib, the risk of death in patients with intermediate or poor risk was reduced by 37% (HR 0.63; 99.8% CI: 0.44 to 0.89; p<0.0001). OS benefits were observed regardless of PD-L1 expression levels. To date, the median OS has not been reached in the group receiving nivolumab combined with low-dose ipilimumab (95% CI: 28.2 months to not estimable [NE]), whereas the median OS in the sunitinib group was 25.9 months.

Meanwhile, the regimen of nivolumab combined with low-dose ipilimumab demonstrated a higher objective response rate (ORR) of 41.6% (95% CI: 36.9 to 46.5; p<0.0001; n=177/425), compared with 26.5% for sunitinib (95% CI: 22.4 to 31.0; n=112/422). The complete response (CR) rate was 9.4% in the nivolumab and low-dose ipilimumab combination group, versus 1.2% in the sunitinib group. Among responders, the median duration of response had not been reached in patients receiving nivolumab plus low-dose ipilimumab (95% CI: 21.8 months to NE), whereas it was 18.2 months in the sunitinib group (95% CI: 14.8 months to NE). Furthermore, the combination of nivolumab and low-dose ipilimumab was associated with a lower incidence of grade 3 or 4 adverse events compared with sunitinib (65% vs. 76%).

“We are delighted that the European Commission has approved the combination of nivolumab and low-dose ipilimumab, based on the significant survival benefit data from the CheckMate-214 clinical study,” said Chris Boerner, Chief Commercial Officer of Bristol-Myers Squibb Company. “This approval will help us further advance our goal of transforming cancer care, improving patients’ quality of life, and achieving long-term survival benefits.”

About CheckMate-214

CheckMate-214 is a randomized, open-label, Phase III clinical study designed to evaluate nivolumab 3 mg/kg combined with ipilimumab 1 mg/kg versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (RCC). In the intermediate- and poor-risk study population, 425 patients received nivolumab 3 mg/kg combined with ipilimumab 1 mg/kg once every 3 weeks for four cycles, followed by sequential nivolumab 3 mg/kg once every 2 weeks. A total of 422 patients received sunitinib 50 mg once daily for 4 weeks, followed by a 2-week rest period before starting the next cycle. The recommended dosage for the combination of nivolumab and low-dose ipilimumab is as follows: nivolumab 3 mg/kg followed by ipilimumab 1 mg/kg, administered via separate intravenous infusions on the same day, with each infusion lasting more than 30 minutes, once every 3 weeks for a total of four doses. After completing the four combination doses, nivolumab should be administered intravenously at 240 mg every 2 weeks (with each infusion lasting more than 30 minutes) or at 480 mg every 4 weeks (with each infusion lasting more than 60 minutes) until disease progression or unacceptable toxicity occurs.

The composite primary efficacy endpoints of this trial were overall survival in intermediate- and high-risk patients, objective response rate (complete response plus partial response), and progression-free survival as determined by the Independent Radiology Review Committee (IRRC). The PD-L1 status of study patients was not considered in this trial.

About Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, causing more than 140,000 deaths worldwide each year. Among these, clear cell renal cell carcinoma is the most prevalent subtype, accounting for approximately 80% to 90% of all RCC cases. The incidence of RCC in men is about twice that in women, with the highest rates observed in North America and Europe. Globally, the 5-year survival rate for diagnosed advanced or metastatic renal cell carcinoma is 8%.

Bristol-Myers Squibb: Advancing the Development of Oncology Research

At Bristol-Myers Squibb, being patient-centric is the guiding principle of all our actions. Our vision is to improve the quality of life and achieve long-term survival for cancer patients. Driven by translational science, we leverage our deep scientific expertise in oncology and immuno-oncology (I-O) research through a unique multidisciplinary collaborative approach, providing personalized innovative treatment solutions to meet diverse patient needs.

Our researchers are dedicated to developing a diverse and targeted drug development pipeline aimed at addressing the complex and specific interactions among tumors, the tumor microenvironment, and the immune system by targeting different immune signaling pathways. We not only pursue internal innovation but also actively promote collaboration and exchange with academia, government entities, patient organizations, and biotechnology companies. Just as immunotherapy (I-O) drugs continue to innovate, we remain committed to continuously supporting patients and fulfilling our promise of transformative medicines.

About Opdivo® (Opdivo™)

OPDIVO™ is a PD-1 immune checkpoint inhibitor that uniquely harnesses the body’s own immune system to help restore anti-tumor immune responses. This mechanism of leveraging the body’s intrinsic immune defenses against cancer has established OPDIVO™ as an important therapeutic option for multiple tumor types.

Leveraging Bristol-Myers Squibb’s scientific expertise in the field of immuno-oncology (I-O) therapy, Opdivo™ boasts a globally leading research and development portfolio that encompasses clinical trials across various phases for multiple tumor types, including Phase III trials. To date, more than 25,000 patients have been enrolled in the clinical development program for Opdivo™. Clinical trials of Opdivo™ help deepen the understanding of the potential implications of biomarkers for patient treatment selection, particularly in identifying how patients with different levels of PD-L1 expression may benefit from Opdivo™.

In July 2014, Opdivo™ became the first PD-1 immune checkpoint inhibitor approved by regulatory authorities worldwide. Currently, Opdivo™ has been approved in more than 65 regions, including the United States, the European Union, Japan, and China. In October 2015, the combination of Opdivo™ and ipilimumab for the treatment of melanoma became the first immuno-oncology (I-O) combination therapy approved by regulatory authorities. It has currently been approved in more than 50 regions, including the United States and the European Union.

On the Collaboration Between Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd.

In 2011, Bristol-Myers Squibb signed a collaboration agreement with Ono Pharmaceutical Co., Ltd. (Ono), obtaining the rights to develop and commercialize nivolumab globally (excluding Japan, South Korea, and Taiwan), while Ono Pharmaceutical retained ownership of the compound at that time. On July 23, 2014, Bristol-Myers Squibb and Ono Pharmaceutical entered into another strategic collaboration agreement for the joint development and commercialization of multiple immuno-oncology agents, including monotherapies and combination therapies, to help address the needs of cancer patients 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, please visit the Bristol-Myers Squibb global website at BMS.com or follow Bristol-Myers Squibb on LinkedIn, Twitter, YouTube and Facebook.

Note: Nivolumab is approved only in mainland China for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are negative for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK), and whose disease has progressed after or who are intolerant to platinum-based chemotherapy. Ipilimumab has not yet been approved for marketing in mainland China.

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