THOUSAND OAKS, Calif. and KENILWORTH, N.J., Dec. 4, 2015 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced a cancer immunotherapy collaboration to support a Phase 1b/3 study investigating BLINCYTO® (blinatumomab) in combination with KEYTRUDA® (pembrolizumab) in patients with diffuse large B-cell lymphoma (DLBCL), which is the most common type of non-Hodgkin lymphoma (NHL). BLINCYTO is Amgen's CD19 bispecific T cell engager (BiTE®), and KEYTRUDA is Merck's anti-PD-1 therapy. The study is an open-label, multicenter, randomized trial to evaluate safety and efficacy in patients with DLBCL.
The companies also announced a second immunotherapy cancer collaboration to support a Phase 1/2 study of AMG 820, Amgen's anti-colony-stimulating factor 1 receptor (CSF1R) antibody, in combination with KEYTRUDA in patients with select advanced solid tumors. The open-label study is designed to evaluate safety and efficacy in patients with select advanced solid tumors, including non-small cell lung, colorectal and pancreatic cancers.
"We are pleased to enter these collaborations with Merck that build upon our growing cancer immunotherapy portfolio," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We look forward to learning more about potential new combination treatment options for BLINCYTO and AMG 820 in disease areas where there remains a high unmet need."
Each immunotherapy is designed to modulate the immune system. BLINCYTO is a bispecific, single-chain antibody construct binding to CD19 and CD3. AMG 820 is a fully human antagonistic IgG2 monoclonal antibody that binds CSF1R and is designed to decrease tumor-associated macrophage (TAM) function. KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.
"The combination of therapies is an important approach for overcoming the ever-changing and complex nature of many cancers," said Dr. Eric Rubin, vice president and therapeutic area head, oncology early-stage development, Merck Research Laboratories. "The combination of these immunotherapies may hold potential for patients with cancer and we look forward to partnering with Amgen to advance these trials with the hope of bringing forward new treatment combinations for patients with various types of cancer."
About Non-Hodgkin Lymphoma
Lymphoma is cancer that begins in cells of the lymph system. The lymph system is part of the immune system, which helps the body fight infection and disease. Because lymph tissue is found throughout the body, lymphoma can begin almost anywhere. The two main types of lymphoma are Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). These can occur in both children and adults. There are many different types of NHL that form from different types of white blood cells (B-cells, T cells, NK cells). Most types of NHL form from B-cells. NHL may be indolent (slow-growing) or aggressive (fast-growing). The most common types of NHL in adults are diffuse large B-cell lymphoma, which is usually aggressive, and follicular lymphoma, which is usually indolent.1
About Non-Small Cell Lung Cancer
Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon, breast and prostate cancers combined. The two main types of lung cancer are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The types are based on the way the cells look under a microscope. NSCLC is much more common than SCLC.2
About Colorectal Cancer
Colorectal cancer (CRC) is cancer that starts in the colon or rectum. Most CRCs are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids). CRC often begins as a growth called a polyp, which may form on the inner wall of the colon or rectum. Some polyps become cancer over time. Finding and removing polyps can prevent CRC.3
About Pancreatic Cancer
The pancreas lies behind the stomach and in front of the spine. There are two kinds of cells in the pancreas. Exocrine pancreas cells make enzymes that are released into the small intestine to help the body digest food. Neuroendocrine pancreas cells (such as islet cells) make several hormones, including insulin and glucagon, which help control sugar levels in the blood.
Most pancreatic cancers form in exocrine cells. These tumors do not secrete hormones and do not cause signs or symptoms. Some types of malignant pancreatic neuroendocrine tumors, such as islet cell tumors, have a better prognosis than pancreatic exocrine cancers.4
About AMG 820
AMG 820 is an investigational human monoclonal antibody that targets the colony-stimulating factor 1 receptor (CSF1R) and is designed to decrease tumor-associated macrophage (TAM) function. It is being investigated as a cancer treatment.
About BLINCYTO® (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.
BiTE® antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body's immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE® antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE® antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.
BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration (FDA), and is now approved in the U.S. for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.
BLINCYTO U.S. Product Safety Information
Important Safety Information Regarding BLINCYTO® (blinatumomab) U.S. Indication
This safety information is specific to the current U.S. approved indication.
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
- Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO® as recommended.
- Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
Contraindications
BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
Warnings and Precautions
Cytokine Release Syndrome (CRS): Life-threatening or fatal CRS occurred in patients receiving BLINCYTO®. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO® as outlined in the Prescribing Information (PI).
Neurological Toxicities: Approximately 50% of patients receiving BLINCYTO® in clinical trials experienced neurological toxicities. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 15% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The median time to onset of any neurological toxicity was 7 days. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO® as outlined in the PI.
Infections: Approximately 25% of patients receiving BLINCYTO® experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO® as needed.
Tumor Lysis Syndrome (TLS): Life-threatening or fatal TLS has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on treatment hydration, should be used during BLINCYTO® treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO® as needed to manage these events.
Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO® infusion and interrupt BLINCYTO® if prolonged neutropenia occurs.
Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO® is being administered.
Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO® treatment. The majority of these events were observed in the setting of CRS. The median time to onset was 15 days. Grade 3 or greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO® treatment. BLINCYTO® treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO®, especially in patients previously treated with cranial irradiation and anti-leukemic chemotherapy. Preparation and administration errors have occurred with BLINCYTO® treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
Adverse Reactions
The most commonly reported adverse reactions ( 20%) in clinical trials were pyrexia (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%), diarrhea (20%) and constipation (20%). Serious adverse reactions were reported in 65% of patients.
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