Myeloflbrosis is a rare blood cancer that disrupts the normal production of blood cells in the human body. Myelofibrosis causes the formation of scar tissue or “fibrosis” in the bone marrow, impairing the bone marrow’s ability to produce healthy red blood cells and platelets. The loss of red blood cells and platelets can lead to anemia and thrombocytopenia, which may cause weakness, fatigue and life-threatening bleeding events.
As the bone marrow makes fewer and fewer healthy red blood cells, abnormal growth of blood-forming cancer cells may occur outside of the bone marrow in organs such as the spleen or liver causing them to become enlarged. An enlarged spleen is common in patients with myelofibrosis, and it may result in abdominal pain/discomfort, a feeling of early fullness and a decreased appetite.
Cancer cells also produce substances called “cytokines” that cause cancer-related inflammation. The abnormal release of these cytokines often results in disease related symptoms such as fatigue, night sweats, itching and fevers.
Patients with myelofibrosis typically need treatment. However, approved therapies only reduce the size of an enlarged spleen and relieve the symptoms associated with the cancer-related inflammation. Unfortunately, current treatments in myelofibrosis have been unsuccessful in restoring normal blood cell production or reversing the cancer driven bone marrow fibrosis.
Navtemadlin (KRT-232) is an investigational therapy that targets a protein called MDM2, offering a potential new treatment for patients with myelofibrosis.
MDM2 is a protein that negatively regulates the activity of a tumor suppressor gene called p53, also known as the “Guardian of the Genome”.
Given the central role of p53 to control the natural lifecycle of cells within the human body, a delicate balance exists between MDM2 and p53. Unfortunately, in myelofibrosis, cancer cells abnormally increase MDM2 levels to shutdown p53 and its ability to fight cancer.
In patients with myelofibrosis, navtemadlin (KRT-232) treatment inhibits the high levels of MDM2 and restores the function of p53 and its ability to kill myelofibrosis cancer cells.
BOREAS is a global Phase 3 registration study for patients with myeloflbrosis whose disease has progressed after treatment with a class of drugs called Janus kinase (JAK) inhibitors.
JAK inhibitors, ruxolitinib or fedratinib, are used in the front line setting for patients with myeloflbrosis and they are the only treatments options currently approved in the United States and Europe. There are no approved therapies in the second line setting for patients with myelofibrosis who are relapsed or refractory to a JAK inhibitor.
BOREAS will compare the efficacy and safety of navtemadlin (KRT-232) versus best available therapy in patients with myelofibrosis whose disease has progressed on or failed to respond to a JAK inhibitor.
Approximately 282 patients will participate in this study including 188 patients randomly assigned to navtemadlin (KRT-232) therapy and 94 patients assigned to best available therapy. For patients randomized to best available therapy, your treating physician will prescribe a therapy appropriate to you.
Before treatment starts, all patients will undergo complete clinical evaluations. Blood samples are collected to ensure the p53 protein is functional and not mutated. In addition, the spleen volume of all patients will be measured using MRI or CT scans and patients will fill out questionnaires to measure their constitutional symptoms. Blood work, imaging and the symptom questionnaire will occur prior to and throughout the study. For the first 24 weeks, patients remain on navtemadlin (KRT-232) or best available therapy unless they cannot tolerate treatment or their disease progresses.
After 24 weeks of treatment, efficacy will be analyzed comparing navtemadlin (KRT-232) to best available therapy using 2 assessments: (1) Spleen-volume reduction from study-start to 24 weeks by MRI or CT, and (2) Patients’ self-reported symptoms from study-start to 24 weeks.
As such, the two key measures of effectiveness for navtemadlin (KRT-232) compared to best available therapy are reduction in spleen-volume and improvement in symptoms after 24 weeks of treatment.
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What is a clinical trial?
A clinical trial is a research study conducted in people with the goal of identifying a new drug or treatment or a new procedure or device. The purpose of a clinical trial is to help doctors identify better or safer ways to treat a disease, or ways to improve the quality of life for patients with a disease. Clinical trials in cancer may be used to test new treatments, new ways to diagnose or prevent cancer, or better ways to manage the symptoms of cancer, as well as the side effects of treatment.
Clinical trials are important because they help doctors to identify new medicines that are more effective and safer than currently available treatments. Over the years, many successful cancer treatments have been identified through clinical trials. Clinical trials help doctors to gain a better understanding of cancer and also provide more options for cancer treatment in the future.
Clinical trials are conducted in a series of steps or phases, with each phase designed to answer specific questions.
Phase 1: These are the first studies of a new drug conducted in people. The main purpose of a phase 1 trial is to find a safe dose for the new treatment and also to decide how the new treatment can be given (by mouth, by injection, etc). Approximately 15-30 patients participate in a phase 1 trial.
Phase 2: A phase 2 trial is conducted to see if the new treatment works in certain types of cancers. Doctors may study whether the cancer shrinks or disappears, how long it takes for the cancer to come back, or whether the new treatment improves quality of life. Between 25 and 100 patients take part in a phase 2 trial.
Phase 3: Before a new treatment receives full regulatory approval, its safety and efficacy must be compared to the current standard treatment in a large study. Patients are randomly assigned (also called randomized) to either the standard treatment or the new treatment. Phase 3 trials typically include several hundred patients.
The BOREAS trial is sponsored by Kartos Therapeutics, a company dedicated to the development of novel, targeted therapeutics that meaningfully improve the lives of patients with cancer. For more information about Kartos Therapeutics, please visit www.kartosthera.com.
Will the costs for participating in the clinical trial be reimbursed?
The costs associated with a clinical trial include doctor visits, hospital stays, cost of drugs, lab tests, X-rays and other imaging tests. These costs may be covered by your health insurance or the study sponsor (in this case, Kartos Therapeutics).
Other costs that you may incur, such as for transportation or housing, may be reimbursed. Please contact your participating cancer center for more information.
What if I experience an adverse event while on a clinical study of navtemadlin (KRT-232)?
if you believe you may have experienced an adverse event while participating in a study that includes navtemadlin (KRT-232), please immediately report this to your physician.
The BOREAS trial will be conducted in approximately 140 cancer centers across at least 20 countries. Please use the interactive map below to locate a cancer center near you where patients are being enrolled to this trial.
Do You Qualify?
Are 18 years of age or older
Have received a diagnosis of myelofibrosis
Were previously treated with ruxolitinib or fedratinib for myelofibrosis and were told that your disease has progressed
Many other conditions must be met before you may participate in the trial. Please contact your nearest participating center. They will be able to give you more information about the requirements for the trial.
If you would like to learn more about BOREAS Clinical Trial for Patients with Myelofibrosis, please fill out the form below.