PRINCETON, NJ, USA I June 6, 2016 I Bristol-Myers Squibb Company (NYSE:BMY) announced today new long-term overall survival (OS) results from two dose-ranging studies, the Phase 1 CA209-003 study and the Phase 2 CA209-010 study, evaluating Opdivo in patients with previously treated advanced renal cell carcinoma (RCC). Findings include the first report of four- and five-year survival data from the advanced RCC cohort (n=34) of study -003, in which OS was an exploratory endpoint. In study -003, 38% of patients were alive at four years, and 34% of patients were alive at five years. In study -010 (n=167), in which OS was a secondary endpoint, 29% of patients were alive at four years. The long-term safety profile of Opdivo in studies -003 and -010 was consistent with previously reported studies, with no new safety signals identified after more than four years of follow-up.
Bristol-Myers Squibb is also presenting additional analyses of health-related quality of life data, a secondary endpoint, from the pivotal, Phase 3 study, CheckMate -025, which evaluated Opdivo versus everolimus in patients with advanced RCC who received prior anti-angiogenic therapy. In this study, 55.4% of patients treated with Opdivo experienced a clinically meaningful improvement in disease-related symptoms, as defined in the study, versus 36.7% of patients treated with everolimus (HR=1.66 [95% CI: 1.33-2.08; p<0.001]).
Dr. Bernard Escudier, Chair of the Genitourinary Oncology Committee, Institut Gustave Roussy in Villejuif, France, commented, “Historically, five-year survival rates for patients diagnosed with advanced kidney cancer have been less than 12%. Building on the survival results seen in the Phase 3 study, CheckMate -025, research evaluating whether Opdivo may provide long-term survival has been of interest to physicians. Data from studies -003 and -010 report, for the first time, longer than four-year survival with Opdivo in previously treated advanced renal cell carcinoma. These findings offer additional important information about the role of Opdivo as a treatment option for these patients.”
The results from studies -003 and -010 will be presented today, Sunday, June 5, at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) during an oral presentation from 10:24 AM – 10:36 AM CDT (Abstract #4507). Data from CheckMate -025 will be presented during a poster session on Monday, June 6, from 1:00 PM – 4:30 PM CDT (Abstract #4549).
“We are excited to share the overall survival results from studies -010 and -003, as these data provide new insights into the long-term efficacy and safety of Opdivo in previously treated advanced renal cell carcinoma,” said Vicki Goodman, M.D., Development Lead, Melanoma and Genitourinary Cancers, Bristol-Myers Squibb. “Additionally, with Opdivo, a meaningful improvement in health-related quality of life, an important factor in cancer care and patient well-being, was observed compared to everolimus, based on new data from CheckMate -025. We look forward to further evaluating our Immuno-Oncology agents across different tumor types, including the Opdivo and Yervoy combination, with the goal of improving long-term survival and quality of life for RCC patients.”
About CA209-003
Study -003, is a Phase 1b open-label, multicenter, multidose, dose-escalation study evaluating Opdivo in 306 patients with select advanced or recurrent malignancies. The primary endpoint was safety and tolerability. Secondary endpoints included objective response rate (ORR). Overall survival (OS) was an exploratory endpoint.
The results from study -003 presented at the 2016 ASCO Annual Meeting focus on the cohort of patients with advanced renal cell carcinoma (RCC, n=34) who had received one to five prior systemic therapies, and were treated with Opdivo 1 mg/kg or 10 mg/kg intravenously every two weeks.
At four years, the OS rate for patients treated with Opdivo was 38%, with a median OS of 22.4 months (95% CI: 12.5-NE), and the five-year survival rate was 34%, with a minimum follow-up of 50.5 months. The long-term safety profile of Opdivo in study -003 was consistent with previous studies, with no new safety signals identified after more than four years of follow-up. Grade 3-4 treatment-related adverse events (AEs) occurred in 17.6% of patients. Any grade treatment-related AEs leading to discontinuation occurred in 8.8% of patients.
About CA209-010
Study -010 is a Phase 2, randomized, dose-ranging study evaluating Opdivo in 167 patients with previously treated advanced renal cell carcinoma (RCC). In the study, patients with advanced RCC who had received prior treatment with one to three therapies (at least one being an anti-angiogenic agent) were treated with Opdivo (0.3, 2 or 10 mg/kg) every three weeks administered intravenously. The primary endpoint was dose-response by progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS) and safety.
At four years, the OS rate for patients treated with Opdivo was 29%, with a median OS of 23.4 months (95% CI: 17.7-26.9), at a minimum follow-up of 49.2 months. In the study, the ORR was 21.6% (95% CI: 15.6-28.6) with a median duration of response lasting 23 months. Median time to response was 2.8 months (1.2-10.0).
The long-term safety profile of Opdivo in study -010 was consistent with previous studies, with no new safety signals identified after approximately four years of follow-up. Grade 3-4 treatment-related adverse events (AEs) occurred in 14.4% of patients in study -010. Any grade treatment-related AEs leading to discontinuation occurred in 9.6% of patients.
About CheckMate -025
CheckMate -025 is an open-label, randomized Phase 3 study of Opdivo versus everolimus in previously treated patients with advanced clear-cell renal cell carcinoma (RCC) after prior anti-angiogenic therapy. Patients were randomized to receive Opdivo (n=410) 3 mg/kg administered intravenously every two weeks or everolimus (n=411) 10 mg administered orally once daily. The primary endpoint of the study was overall survival (OS). Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), quality of life (QoL) and safety. Patient-reported QoL was measured using the kidney specific, Functional Assessment of Cancer Therapy–Kidney Symptom Index–Disease Related Symptoms (FKSI-DRS) scale, and European Quality of Life (EuroQol)-5 Dimensions (EQ-5D) questionnaire. Quality of life was measured at baseline among approximately 361 patients randomized for treatment with Opdivo and 343 patients randomized for treatment with everolimus.
A higher proportion of patients treated with Opdivo experienced a clinically meaningful improvement in health-related QoL (defined as a 2-point increase from baseline using FKSI-DRS) compared to patients treated with everolimus (200 [55.4%] of 361 vs. 126 [36.7%] of 343, respectively; (HR=1.66 [95% CI: 1.33-2.08; p<0.001]). Median time to improvement in disease-related symptoms occurred at 4.7 months (95% CI: 3.7-7.5) with Opdivo and was not estimable with everolimus due to a limited number of patients who experienced improvement.
About Renal Cell Carcinoma
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, accounting for more than 100,000 deaths worldwide each year. Clear-cell RCC is the most prevalent type of RCC and constitutes 80% to 90% of all cases. RCC is approximately twice as common in men as it is in women, with the highest rates of the disease found in North America and Europe. Globally, the five-year survival rate for those diagnosed with advanced kidney cancer is 12%.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, we have a vision for the future of cancer care that is focused on Immuno-Oncology, now considered a major treatment choice alongside surgery, radiation, chemotherapy and targeted therapies for certain types of cancer.
We have a comprehensive clinical portfolio of investigational and approved Immuno-Oncology agents, many of which were discovered and developed by our scientists. Our ongoing Immuno-Oncology clinical program is looking at broad patient populations, across multiple solid tumors and hematologic malignancies, and lines of therapy and histologies, with the intent of powering our trials for overall survival and other important measures like durability of response. We pioneered the research leading to the first regulatory approval for the combination of two Immuno-Oncology agents, and continue to study the role of combinations in cancer.
We are also investigating other immune system pathways in the treatment of cancer including CTLA-4, CD-137, KIR, SLAMF7, PD-1, GITR, CSF1R, IDO, and LAG-3. These pathways may lead to potential new treatment options – in combination or monotherapy – to help patients fight different types of cancers.
Our collaboration with academia, as well as small and large biotech companies, to research the potential of Immuno-Oncology and non-Immuno-Oncology combinations, helps achieve our goal of providing new treatment options in clinical practice.
At Bristol-Myers Squibb, we are committed to changing survival expectations in hard-to-treat cancers and the way patients live with cancer.
About Opdivo
Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Opdivo is a PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 expressed on activated T-cells, and blocks the binding of PD-L1 and PD-L2, preventing the PD-1 pathway’s suppressive signaling on the immune system, including the interference with an anti-tumor immune response.
Opdivo’s broad global development program is based on Bristol-Myers Squibb’s understanding of the biology behind Immuno-Oncology. Our company is at the forefront of researching the potential of Immuno-Oncology to extend survival in hard-to-treat cancers. This scientific expertise serves as the basis for the Opdivo development program, which includes a broad range of Phase 3 clinical trials evaluating overall survival as the primary endpoint across a variety of tumor types. The Opdivo trials have also contributed toward the clinical and scientific understanding of the role of biomarkers and how patients may benefit from Opdivo across the continuum of PD-L1 expression. To date, the Opdivo clinical development program has enrolled more than 18,000 patients.
Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world in July 2014, and currently has regulatory approval in 51 countries including the United States, Japan, and in the European Union.
U.S. FDA APPROVED INDICATIONS FOR OPDIVO®
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. 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 patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. 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 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 advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post- transplantation brentuximab vedotin. 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.
Please refer to the end of the Important Safety Information for a brief description of the patient populations studied in the Checkmate trials.
About the Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono) 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, Bristol-Myers Squibb and Ono 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 and Facebook.
SOURCE: Bristol-Myers Squibb
