CFI-402257, a Potent and Selective TTK Inhibitor, in Solid Tumors and With Fulvestrant in Breast Cancer

This is an interventional treatment trial for Advanced Solid Tumor focused on measuring advanced solid tumors, advanced breast cancer, CFI-402257, 2257, fulvestrant, TWT-203, TWT203, UHN, University Health Network, Treadwell, Treadwell Therapeutics, endocrine therapy, TTK, TTK inhibitor Read More

Inclusion Criteria: Part A

1. Have histological or cytological proof of advanced cancer that has progressed on at least 1 prior line of systemic therapy.
2. Have measurable or nonmeasurable disease as per RECIST 1.1 guidelines or other appropriate disease assessment guidelines.
3. Are ≥18 years of age.
4. Have clinically acceptable laboratory screening results (i.e., clinical chemistry, hematology, and urinalysis) within certain limits specified.
5. Have an ECOG performance status of 0 or 1.
6. Be able to swallow oral medications.
7. Have a life expectancy of greater than 3 months.
8. Women and men of childbearing potential must agree to use highly effective means of contraception.
9. A negative serum pregnancy test within 72 hours prior to the initiation of protocol therapy..
10. Can understand the requirements of the study, provide written informed consent.

Inclusion Criteria: Part B

1. Have histologically and/or cytologically confirmed diagnosis of breast cancer positive for estrogen receptor (ER) and/or progesterone receptor (PR) and negative for HER2 for which no curative therapy exists.

2. Prior therapy:

   • Must have previously received at least 1 and no more than 3 lines of endocrine therapy (ET), either as monotherapy or as a combination therapy with CDK4/6 inhibitor for breast cancer.
   • Must have progressed during or within 28 days of completion of prior treatment with a CDK4/6 inhibitor in combination an AI or tamoxifen.
   • Must have received no more than 1 line of cytotoxic chemotherapy in the advanced/metastatic setting.
3. Have measurable or nonmeasurable disease as per RECIST 1.1 guidelines.
4. Are female or male
5. Are ≥18 years of age
6. Are postmenopausal. Premenopausal or perimenopausal patients are required to receive goserelin for at least 4 weeks before the start of study drug.
7. Have clinically acceptable laboratory screening results (i.e., clinical chemistry, hematology, and urinalysis) within certain limits.
8. Have an ECOG performance status of 0 or 1.
9. Be able to swallow oral medications.
10. Have a life expectancy greater than 3 months.
11. Women of childbearing potential must agree to use highly effective means of contraception.
12. A negative serum pregnancy test within 72 hours prior to the initiation of protocol therapy will be required for women of childbearing potential.
13. Can understand the requirements of the study, provide written informed consent.

Exclusion Criteria: All Parts

1. Are pregnant or nursing.
2. Have received chemotherapy, biological therapy, or investigational treatment less than 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study drug. Have received radiotherapy less than 2 weeks prior to first dose of study drug.
3. Received growth factors within 14 days prior to initiation of dosing of CFI-402257 or who will require ongoing treatment with growth factors
4. Have active, acute, or clinically significant chronic infections.

5. Have the following cardiovascular conditions

   • Have uncontrolled severe hypertension
   • Have symptomatic congestive heart failure
   • Have active angina pectoris or recent myocardial infarction
   • Have chronic atrial fibrillation or QTc of greater than 470 msec.
6. Have had major surgery within 21 days of starting therapy.
7. Primary central nervous system malignancies or known central nervous system metastasis.
8. Being treated with full dose warfarin.
9. Coagulopathy or any history of coagulopathy within the past 6 months, including history of deep vein thrombosis or pulmonary embolism.
10. Patients must avoid the use of CYP3A sensitive substrates, PgP, BCRP inhibitors prior to the first dose of CFI-402257.
11. Have had prior treatment with a TTK/MPS1 inhibitor.
12. Part B only: Known bleeding disorder which would prohibit administration of fulvestrant.
13. Part B only: Concomitant active malignancy other than ER+/HER2- advanced breast cancer.
14. Part A only: Concomitant active malignancy other than primary malignancy