Bristol-Myers Squibb Release: First Presentation Of Efficacy Data From Checkmate -204 Evaluating The Combination Of Opdivo (Nivolumab) And Yervoy (Ipilimumab)Demonstrates Anti-Tumor Activity In Advanced Melanoma Patients With Brain Metastases

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced efficacy and safety data from CheckMate -204, the first Phase 2 study to evaluate Opdivo plus Yervoy as a potential treatment for patients with melanoma metastatic to the brain. The primary endpoint of intracranial (IC) clinical benefit rate (CBR), defined as complete response plus partial response plus stable disease = 6 months, was 60% (95% CI: 48 to 71) at the median follow-up of 9.2 months among the 75 evaluated patients. These data will be presented during an oral session today from 10:12 – 10:24 a.m. CDT during the Melanoma/Skin Cancers session in the Arie Crown Theater at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017.

“These results from the CheckMate -204 trial are the first efficacy data investigating the use of an Immuno-Oncology combination for the treatment of patients with untreated melanoma brain metastases. The use of upfront systemic therapy is a novel approach in this population where radiation therapy is the norm.”

“More than 60 percent of patients with stage IV melanoma eventually develop brain metastases, which are a major cause of illness and death among these patients,” said Hussein Tawbi, M.D., PhD, Associate Professor, Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center. “These results from the CheckMate -204 trial are the first efficacy data investigating the use of an Immuno-Oncology combination for the treatment of patients with untreated melanoma brain metastases. The use of upfront systemic therapy is a novel approach in this population where radiation therapy is the norm.”

A complete IC response was achieved by 21% (n=16) of patients; 33% (n=25) had partial responses; and 5% (n=4) experienced stable disease. The IC objective response rate (ORR) was 55% (95% CI: 43 to 66) with a safety profile consistent with previously reported data in melanoma patients without brain metastases. Treatment-related grade 3/4 adverse events (AEs) occurred in 52% of patients (n=39), with 8% (n=6) being neurologic in nature, including headaches. Three treatment-related deaths were reported as cardiogenic shock, IC hemorrhage and malignant neoplasm progression.

“The CheckMate -204 trial is important because research about therapies for advanced melanoma patients with brain metastases is somewhat limited. Until recently, these patients have been excluded from clinical trials,” said Vicki Goodman, M.D., development lead, Melanoma and Genitourinary Cancers, Bristol-Myers Squibb. “These data add to the body of scientific knowledge on Opdivo and Yervoy and highlight our continued commitment to researching the potential benefits of this combination in a diverse set of patient groups.”

CheckMate -204 is a Phase 2 open-label study in 75 patients with melanoma that had spread to the brain, resulting in one or more asymptomatic brain metastases of 0.5 to 3.0 cm. The trial evaluated the efficacy and safety of Opdivo in combination with Yervoy followed by Opdivo monotherapy. The primary endpoint was IC CBR. Secondary objectives included overall survival, extracranial CBR and safety.

Enrolled patients received Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four doses, followed by Opdivo 3 mg/kg every two weeks until disease progression or toxicity. Patients who experienced severe AEs during the combination treatment could receive Opdivo monotherapy when their toxicity resolved, and stereotactic radiotherapy was permitted for patients experiencing brain oligo-progression if an assessable brain metastasis remained. The median number of combination doses was three (range 1 to 4), and 28 patients (37%) received four combination induction doses and 42 patients (56%) began Opdivo maintenance (median 12 doses, range 1 to 36).

About Metastatic Melanoma

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 steadily for the last 30 years. In the United States, 87,000 new diagnoses of melanoma and more than 9,700 related deaths are estimated for 2017. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 388,262, with 98,288 related deaths. Melanoma is mostly curable when treated in its early stages. However, patients in the United States diagnosed with advanced melanoma classified as Stage IV historically have a five-year survival rate of 15% to 20% and 10-year survival of about 10% to 15%.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research

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 for hard-to-treat cancers that could potentially improve outcomes for these patients.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies 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 how patients’ individual tumor biology can be used as a guide for treatment decisions throughout their journey.

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.

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 60 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 50 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 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.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

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 patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.

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 patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of =7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.