THOUSAND OAKS, Calif., Dec. 2, 2019 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced new clinical data from its oncology in-line products and pipeline that will be presented at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Dec. 7-10, 2019.
The Phase 3 CANDOR study, which was accepted as a late-breaking abstract, evaluated KYPROLIS® (carfilzomib) in combination with dexamethasone and DARZALEX® (daratumumab) (KdD) compared to KYPROLIS and dexamethasone alone (Kd) in patients with relapsed or refractory multiple myeloma. Additional data from Amgen's hematology franchise will include new results from the bispecific T cell engager (BiTE®) platform across multiple blood cancers, including multiple myeloma, acute myeloid leukemia, acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma and non-Hodgkin's lymphoma.
"The late-breaking abstract from the CANDOR study evaluating KYPROLIS with an anti-CD38 monoclonal antibody demonstrates that by combining these two powerful agents, this regimen has the potential to be practice-changing for the treatment of patients with relapsed or refractory multiple myeloma," said David M. Reese, M.D., executive vice president of Research and Development at Amgen.
Additionally, data from study AALL1331 conducted by the Children's Oncology Group (COG) evaluating BLINCYTO® (blinatumomab) versus chemotherapy in first relapse of childhood B-lymphoblastic leukemia (B-ALL) were accepted as a late-breaking abstract. AALL1331 is sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute (NCI), part of the National Institutes of Health, and is conducted by the NCI-funded COG. Amgen provided BLINCYTO for the study under a Collaborative Research and Development Agreement between the NCI and Amgen. BLINCYTO, which was approved in 2014, is the first and only approved BiTE molecule.
"The data being presented at ASH demonstrate our commitment to furthering the science of our in-line products, including KYPROLIS and BLINCYTO, while also advancing our pipeline of innovative BiTE molecules which could potentially provide new treatment approaches for patients across blood cancers for which there remains high unmet need," continued Reese.
A complete listing of Amgen's abstracts is available on the ASH website. Notable abstracts include:
KYPROLIS Amgen Sponsored Abstracts
KYPROLIS Investigator Led Abstracts
BLINCYTO Amgen Sponsored Abstracts
BLINCYTO Investigator Led Abstracts
CANDOR, a randomized, open-label Phase 3 study of KYPROLIS, dexamethasone and DARZALEX (KdD) compared to KYPROLIS and dexamethasone (Kd), has evaluated 466 relapsed or refractory multiple myeloma patients who have received one to three prior therapies. Patients were treated until disease progression. The primary endpoint was PFS, and the key secondary endpoints were overall response rate, minimal residual disease and overall survival. PFS was defined as time from randomization until disease progression or death from any cause.
In the first arm, patients received KYPROLIS twice weekly at 56 mg/m2 and dexamethasone in combination with DARZALEX. In the second arm (control), patients received KYPROLIS twice weekly at 56 mg/m2 and dexamethasone.
CANDOR was initiated as part of a collaboration with Janssen, and under the terms of the agreement, Janssen co-funded the study. For more information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT03158688.
About the COG AALL1331 Study
The COG AALL1331 study is a risk-stratified, randomized, Phase 3 trial of blinatumomab in first relapse of pediatric B-ALL to evaluate disease-free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapsed B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab. It also compares the DFS of low risk (LR) relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab. Key secondary endpoints include overall survival of HR, IR, and LR relapsed B-ALL patients. This is a global study that is being conducted in Australia, Canada, New Zealand and United States. Click here to read about the trial on ClinicalTrials.gov.
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.1 It is a rare and life-threatening disease that accounts for approximately one percent of all cancers.2,3 Worldwide, approximately 160,000 people are diagnosed with multiple myeloma each year, and 106,000 patient deaths are reported on an annual basis.2
About KYPROLIS® (carfilzomib)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.4 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.5 In some cells, KYPROLIS can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.4,5
Since its first approval in 2012, more than 125,000 patients worldwide have received KYPROLIS. KYPROLIS is approved in the U.S. for the following:
KYPROLIS is also approved in Algeria, Argentina, Australia, Bahrain, Belarus, Brazil, Canada, Chile, Colombia, Ecuador, Egypt, European Union, Hong Kong, India, Israel, Japan, Jordan, Kuwait, Lebanon, Macao, Malaysia, Mexico, Morocco, New Zealand, Oman, Philippines, Qatar, Russia, Saudi Arabia, Singapore, S. Korea, Switzerland, Taiwan, Thailand, Turkey and United Arab Emirates.
Important U.S. KYPROLIS® (carfilzomib) Safety Information
Acute Renal Failure
Tumor Lysis Syndrome
Hepatic Toxicity and Hepatic Failure
Posterior Reversible Encephalopathy Syndrome (PRES)
Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients
Please see full Prescribing Information at www.kyprolis.com.
About ALL and MRD
ALL is a rapidly progressing cancer of the blood and bone marrow that occurs in both adults and children.6,7 Poor outcomes have been observed in patients who achieve first or second complete hematologic remission but are persistently MRD-positive, which currently remains detectable at the molecular level after treatment.8,9 For more information about MRD, please visit AmgenOncology.com.
About BiTE® Technology
Bispecific T cell engager (BiTE®) technology is a targeted immuno-oncology platform that is designed to engage patients' own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform leads to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential.
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 and is approved in the U.S. for the treatment of:
In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:
IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
Warnings and Precautions
Dosage and Administration Guidelines
Please see full Prescribing Information and medication guide for BLINCYTO at www.BLINCYTO.com.
About Multiple Myeloma and Bone Complications
Multiple myeloma is the second most common hematologic cancer, and it develops in plasma cells located in the bone marrow microenvironment.2,10 It is typically characterized by osteolytic bone lesions as well as renal failure, which are both part of diagnosis (CRAB criteria).11 Each year an estimated 160,000 new cases of multiple myeloma are diagnosed worldwide, resulting in more than 106,000 deaths per year.2
More than 90 percent of patients develop osteolytic lesions during the course of the disease.12 Preventing bone complications is a critical aspect of caring for patients with multiple myeloma, because these events can result in significant morbidity.13 Current treatment options to prevent bone complications are limited to bisphosphonates, including zoledronic acid, which are cleared through the kidneys.14 Approximately 60 percent of all multiple myeloma patients have or will develop renal impairment over the course of the disease.15
About XGEVA® (denosumab)
XGEVA targets the RANKL pathway to prevent the formation, function and survival of osteoclasts, which break down bone. XGEVA is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. XGEVA is also indicated for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity and for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.
XGEVA® is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. XGEVA® is indicated for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. XGEVA® is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.
IMPORTANT SAFETY INFORMATION
Important Safety Information
Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®. XGEVA® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels, especially in the first weeks of initiating therapy, and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when XGEVA® is administered with other drugs that can also lower calcium levels. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake.
XGEVA® is contraindicated in patients with known clinically significant hypersensitivity to XGEVA®, including anaphylaxis that has been reported with use of XGEVA®. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue XGEVA® therapy permanently.
Drug Products with Same Active Ingredient
Patients receiving XGEVA® should not take Prolia® (denosumab).
Osteonecrosis of the Jaw
Osteonecrosis of the jaw (ONJ) has been reported in patients receiving XGEVA®, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with cancer, the incidence of ONJ was higher with longer duration of exposure.
Patients with a history of tooth extraction, poor oral hygiene, or use of a dental appliance are at a greater risk to develop ONJ. Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections.
Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA® and periodically during XGEVA® therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA®. Consider temporarily interrupting XGEVA® therapy if an invasive dental procedure must be performed.
Patients who are suspected of having or who develop ONJ while on XGEVA® should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.
Atypical Subtrochanteric and Diaphyseal Femoral Fracture
Atypical femoral fracture has been reported with XGEVA®. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution.
Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During XGEVA® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of XGEVA® therapy should be considered, pending a risk/benefit assessment, on an individual basis.
Hypercalcemia Following Treatment Discontinuation in Patients with Giant Cell Tumor of Bone (GCTB) and in Patients with Growing Skeletons
Clinically significant hypercalcemia requiring hospitalization and complicated by acute renal injury has been reported in XGEVA®-treated patients with GCTB and in patients with growing skeletons within one year of treatment discontinuation. Monitor patients for signs and symptoms of hypercalcemia after treatment discontinuation and treat appropriately.
Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation
Multiple vertebral fractures (MVF) have been reported following discontinuation of treatment with denosumab. Patients at higher risk for MVF include those with risk factors for or a history of osteoporosis or prior fractures. When XGEVA® treatment is discontinued, evaluate the individual patient's risk for vertebral fractures.
XGEVA® can cause fetal harm when administered to a pregnant woman. Based on findings in animals, XGEVA® is expected to result in adverse reproductive effects.
Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of XGEVA®. Apprise the patient of the potential hazard to a fetus if XGEVA® is used during pregnancy or if the patient becomes pregnant while patients are exposed to XGEVA®.
The most common adverse reactions in patients receiving XGEVA® with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia.
For multiple myeloma patients receiving XGEVA®, the most common adverse reactions were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache. The most common serious adverse reaction was pneumonia. The most common adverse reaction resulting in discontinuation of XGEVA® was osteonecrosis of the jaw.
The most common adverse reactions in patients receiving XGEVA® for giant cell tumor of bone were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. The most common serious adverse reactions were osteonecrosis of the jaw and osteomyelitis.
The most common adverse reactions resulting in discontinuation of XGEVA® were osteonecrosis of the jaw and tooth abscess or tooth infection.
The most common adverse reactions in patients receiving XGEVA® for hypercalcemia of malignancy were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.
Please visit www.xgeva.com for Full U.S. Prescribing Information.
About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient's life – not just their cancer journey – so they can take control of their lives.
For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company's history, moving with great speed to advance those innovations for the patients who need them.
At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.
For more information, follow us on www.twitter.com/amgenoncology.
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
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