CFI-402257 is an oral drug that blocks TTK protein kinase (also known as Monopolar spindle 1
[Mps1]) activity. TTK is a protein that is important in regulating cell growth, and cell
death, and ensuring proper division. Many tumors are shown to make too much TTK. When there
is too much TTK produced, it is believed to contribute to uncontrolled cancer cell growth and
division leading to additional mutations in cancer cells. Therefore, it is believed that
blocking this protein from working will lead to cancer cell death, stopping tumors from
growing or shrinking them.
This study will have two parts: dose escalation and dose expansion.
The dose escalation part will test different dose levels of study drug in groups of patients
to find the highest dose of study drug that can be given safely to patients (called maximum
tolerated dose or MTD).
The expansion part will further assess the safety, tolerability, and PK of the MTD found in
the escalation part of the study in additional group of patients.
- Have histological or cytological proof of advanced cancer that has progressed and for
which there is no further standard anticancer therapy available in the opinion of the
- Patients must have measurable disease as per RECIST v 1.1 guidelines.
- Patients must be ≥18 years of age.
- Have clinically acceptable laboratory screening results (i.e., clinical chemistry,
hematology, and urinalysis) within certain limits.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Be able to swallow oral medications.
- Have a life expectancy of greater than 3 months.
- Women and men of child-producing potential must agree to use highly effective means of
contraception for a specified period.
- A negative serum pregnancy test for women of childbearing potential.
- Have the ability to understand the requirements of the study, provide written informed
consent which includes authorization for release of protected health information,
abide by the study restrictions, provide archived tissue if available for biomarker
studies, provide a blood sample for genetic testing and agree to return for the
- Women who are pregnant or nursing.
- Have received radiotherapy (patients having limited field palliative radiotherapy less
than 2 weeks), chemotherapy, biological therapy, or investigational treatment less
than four weeks (six weeks for nitrosoureas or mitomycin C) prior to first dose of
study drug or have not recovered from all acute toxicities from prior treatments and
those deemed by the Investigator not to affect safety assessment.
- Patients who have received growth factors within 14 days prior to initiation of dosing
of CFI-402257 or who will require ongoing treatment with growth factors throughout the
duration of the trial.
- Have active, acute, or clinically significant chronic infections.
- Have uncontrolled severe hypertension.
- Have symptomatic congestive heart failure.
- Have active angina pectoris or recent myocardial infarction (within 6 months).
- Have chronic atrial fibrillation or QTc of greater than 470 msec.
- Have had major surgery within 21 days of starting therapy.
- Have additional uncontrolled serious medical or psychiatric illness.
- Have any medical condition that would impair the administration of oral agents
including significant bowel resection, inflammatory bowel disease or uncontrolled
nausea or vomiting.
- Known central nervous system metastasis.
- Patients being treated with full dose warfarin are excluded.
- Patients being treated with the following drugs are excluded: Alfentanil, Pimozide,
Cyclosporine, Quinidine, Digoxin, Sirolimus, Dihydroergotamine, Tacrolimus,
Ergotamine, Warfarin, Fentanyl.