Treatment Study for Subjects with Myelofibrosis Who Have Failed a JAK Inhibitor

Myelofibrosis (MF) belongs to a group of closely related blood cancers known as “myeloproliferative neoplasms (MPNs)” in which the bone marrow cells that produce the body’s blood cells develop and function abnormally. The result is excessive fibrous (scar) tissue formation in the bone marrow, which can lead to severe anemia, weakness, fatigue and enlarged spleen and liver.

MF can occur on its own, called “primary myelofibrosis (PMF)” or as a progression of other bone marrow diseases (called “post”). Other MPNs that can progress to myelofibrosis include polycythemia vera (PV) and essential thrombocythemia (ET). Polycythemia vera (PV) is a bone marrow disease that leads to an abnormal increase in the number of blood cells. The red blood cells are mostly affected. Essential thrombocythemia (ET) is a disease in which too many platelets are made in the blood and bone marrow. The characteristics of MF, post-PV-MF and post-ET-MF are virtually identical and treatment is generally the same for all three.

KRT-232 is a small molecule inhibitor and can reverse a mechanism through which unhealthy or tumor cells can survive and grow. This study will test if KRT-232 can restore the function of your healthy bone marrow cells and reduce the symptoms of MF. There are 2 parts planned for this study, Part A will test different doses and schedules of KRT-232 in 3 groups of participants to identify the recommended dose and schedule for Part B. Part B will continue to test if the recommended dose and schedule is a tolerable and effective treatment for MF.

In order to participate you must meet the following criteria:

• Are 18 years of age or older.
• Have a diagnosis of PMF, post-PV-MF, or post-ET-MF with a classification of high-risk, intermediate-2 risk, or intermediate-1 risk as defined by the Dynamic International Prognostic System (DIPSS).
• Have adequate organ function.
• Have disease that has not responded to treatment with a JAK inhibitor or your disease recurred or did not respond to treatment with ruxolitinib.

You will be excluded from the study if any of the following criteria apply to you:

• Have disease that tests positive for p53 mutations.
• Have had a splenectomy (removal of your spleen).
• Have had an allogeneic stem-cell transplantation or you are eligible for an allogeneic stem-cell transplantation.
• Have received prior treatment with MDM2 inhibitor therapy or p53-directed therapy.

This is a partial list of eligibility requirements. To inquire about your eligibility, please call the contact number provided. If you wish to inquire via email, please include the title of the study in your message.