PRINCETON, NJ, USA I November 12, 2016 I Bristol-Myers Squibb Company (NYSE:BMY) today announced safety and efficacy data from a Phase 1/2 study of urelumab in combination with Opdivo (nivolumab) in patients with hematologic and solid tumors, including biomarker analyses by level of PD-L1 expression. The combination of urelumab and Opdivo showed encouraging efficacy among 46 evaluable melanoma patients with an objective response rate (ORR) of 50% (23/46 with 18 confirmed and 5 unconfirmed). ORR was a secondary endpoint as measured by Response Evaluation Criteria In Solid Tumors (RECIST). Similar response was seen in both PD-L1 positive and PD-L1 negative melanoma patients, with ORR of 50% (10/20) and 47% (8/17) in those with ≥1% and <1% PD-L1 expression, respectively. Among the other cohorts (n=78), one non-small cell lung cancer (NSCLC) patient and one squamous cell carcinoma of the head and neck (SCCHN) patient had an objective response. In the full patient population (n=138), no significant added toxicity was observed with urelumab in combination with Opdivo over Opdivo monotherapy. These data were presented at an oral presentation (poster number 239) at the Society for Immunotherapy of Cancer (SITC) 31 Annual Meeting on November 12 at 10:40 a.m. EST in National Harbor, Maryland.
The overall rate of treatment-related adverse events (TRAEs) was 63% (n=87), with the most common being fatigue (31%), ALT increased (11%), anemia (10%), and AST increased (9%). No additional signals were seen with the combination therapy compared to Opdivo monotherapy. The rate of Grade 3-4 TRAEs was 17% (n=23). The rate of discontinuations due to TRAEs was 6% (n=8).
Urelumab is a fully human monoclonal IgG4k antibody agonist of CD137, a tumor necrosis factor (TNF) family receptor expressed primarily on activated T cells and activated natural killer (NK) cells. Opdivo blocks the inhibitory function of the PD-1 receptor on T cells.
“These results suggest that urelumab in combination with Opdivo may offer an antitumor benefit in patients with melanoma, in both PD-L1 expressors and non-expressors,” said Erminia Massarelli, MD, PhD, MS, Associate Clinical Professor at the City of Hope Comprehensive Cancer Center. “While there have been major advances in melanoma treatment over the past five years, some patients continue to need additional options to treat the disease, which is one of deadliest forms of cancer.”
“We are committed to exploring complementary immune pathways and mechanisms and look forward to continued study of urelumab in combination with multiple Immuno-Oncology agents across various tumor types and personalized to patient biologies,” said Tim Reilly, head of Oncology Early Assets Development at Bristol-Myers Squibb.
About the Study
The Phase 1/2 study of urelumab administered in combination with Opdivo evaluated which doses are safe and tolerable. Efficacy was evaluated in advanced/metastatic melanoma (n=46), diffuse large B-cell lymphoma (DLBCL, n=19), NSCLC patients who had progressed on a PD-1/PD-L1 therapy (n=14), NSCLC patients who had not previously received a PD-1/PD-L1 therapy (n=20), SCCHN (n=22) and other tumors (n=3). The ORR for these cohorts was 50%, 0%, 0%, 5%, 5% and 0%, respectively, and the disease control rate (DCR) was 70%, 21%, 21%, 35%, 23% and 33%, respectively.
After an initial phase where patients received urelumab 3 mg IV every four weeks plus Opdivo 3 mg/kg IV every two weeks, patients were treated with urelumab 8 mg IV every four weeks plus Opdivo 3 mg/kg IV every two weeks. Cohort expansion, during which patients with specific tumor types received urelumab 8 mg IV every four weeks plus Opdivo 240 mg IV every two weeks, was initiated after completion of the required safety monitoring period.
The primary endpoint of the Phase 1/2 study is safety, as measured by the rate of adverse events (AEs) and serious adverse events (SAEs). All subjects who received at least one (full or partial) dose of urelumab or Opdivo were evaluated for safety during treatment and for up to 100 days follow-up (n=138). Secondary outcome measures include best overall response, ORR, duration of response and progression free survival rate.
About Metastatic Melanoma1
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease, and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing for at least 30 years. Approximately 73,870 melanoma cases were estimated to be diagnosed in the U.S. in 2015. Melanoma is mostly curable when treated in its early stages. However, in its late stages, 5-year and 10-year survival rates in the U.S. average 15-20% and 10-15%, respectively.
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 enrolled more than 25,000 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 57 countries, including the United States, the European Union and Japan. 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 47 countries, including the United States and 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 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 the confirmatory trials
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.
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.
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.
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.
Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents – including the first combination of two I-O agents in metastatic melanoma – and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 12 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part, but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.
1 American Cancer Society. Melanoma Skin Cancer. http://www.cancer.org/acs/groups/cid/documents/webcontent/003120-pdf.pdf. Updated November 10, 2015. Accessed January 20, 2016.
SOURCE: Bristol-Myers Squibb
