What we are studying
This is a research Study and does not constitute treatment or therapy. INCB057643 (Study Drug) is an investigational drug that is being studied by Incyte Corporation (the Sponsor of the research study) for use in the treatment in people who have advanced cancer. “Investigational” means that INCB057643 has not been approved by the US Food and Drug Administration (FDA) or any other regulatory agencies outside of the US for use as a prescription or over-the-counter medication.
INCB057643 works by inhibiting, or blocking, the activity of a family of proteins called the bromodomain and extra-terminal (BET) proteins. BET proteins play an important role in helping your genes (a part of your DNA, also known as deoxyribonucleic acid) make, or express, other proteins, some of which are responsible for driving the growth, replication, and survival of cells. Sometimes, BET proteins are also involved with helping genes that cause cancer, called oncogenes. When BET proteins are stopped from working, it may lead to a decrease in expression of these oncogenes, which in turn may slow or stop the growth of some cancer cells.
The purpose of the Study is to assess the safety and tolerability of INCB057643 as a monotherapy for subjects with advanced malignancies and to select doses that will be studied further.
Other purposes of this study are:
• To study the way INCB057643 enters and leaves the body and tissues over time (known as pharmacokinetics),
• To study the effect food has on how INCB057643 enters and leaves the body and tissues over time (known as food effect),
• To study how INCB057643 acts on and in the body (known as pharmacodynamics),
• To study the effect INCB057643 has on your disease status and whether it reduces the number of cancer cells in your body,
• To identify subgroups of patients with certain types of advanced cancer who may benefit most from INCB057643.
The Study will be conducted at approximately 15 sites in the US. This is an “open label” study. This means that you and the study research staff will know that you are receiving INCB057643. The length of your participation in the Study is expected to be about 6 months; this may vary widely depending on your specific disease.
There are two parts to this study,
Part 1 – Dose Escalation
Subjects in Part 1 will be in the dose escalation part of the Study with INCB057643 in three disease specific treatment groups.
o Treatment Group A (TGA) will include subjects with any advanced solid tumor or lymphoma.
o Treatment Group B (TGB) will include subjects with leukemia or myelodysplastic syndrome (MDS).
o Treatment Group C (TGC) will include subjects with multiple myeloma (MM), myelodysplastic/myeloproliferative neoplasms (MDS/MPN) or myelofibrosis (MF).
Dose escalation is when one cohort (a small set of subjects) is given a certain amount of INCB057643 and evaluated for side effects before giving a higher dose of INCB057643 to the next cohort. Dose escalation will be used to find the maximum dose of INCB057643 that is tolerated in the body. Each cohort will be observed for a minimum number of days on treatment (21 days) before the next cohort starts at the next dose level.
The cohorts will initially consist of a minimum of 3 subjects each. The doses will be increased in each new cohort until a certain level of toxicity is observed. If a dose limiting toxicity (side effects during the study that are severe enough to prevent increasing the dose level), occurs within a cohort, that cohort may enroll at least 3 additional subjects to further evaluate the safety of the dose. Your Study Doctor will monitor your symptoms and lab tests to determine if you have a dose limiting toxicity.
After a safe dose of INCB057643 has been determined during the Part 1 dose escalation phase of the Study, three additional treatment groups will be enrolled into the Part 2 dose expansion phase of the Study to further assess the safety and tolerability of INCB057643.
• Part 2 – Dose Expansion
Approximately 95 additional subjects with specific tumor types will be enrolled into three treatment groups (detailed below). The dose of INCB057643 given will be determined during the dose escalation portion in Part 1.
o Treatment Group A (TGA) will include subjects with the following tumor types:
? Pancreatic cancer,
? Colorectal cancer,
? Non-small cell lung cancer,
? Prostate cancer,
? Triple-negative breast cancer,
? Ovarian cancer,
? Glioblastoma (Brain Cancer),
? NUT midline carcinoma,
? Non-Hodgkin’s lymphoma, or
? Any other type of solid tumor or lymphoma in which BET proteins may play a role in helping the tumor cells survive and grow.
o Treatment Group B (TGB) will include subjects with acute myeloid leukemia (AML) or MDS.
o Treatment Group C (TGC) will include subjects with MM, MDS/MPN, or MF.