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

Prior treatment

• 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.
• Received growth factors within 14 days prior to initiation of dosing of CFI-402257 or who will require ongoing treatment with growth factors
• Have had major surgery within 21 days of starting therapy.
• Being treated with full dose warfarin.
• Patients must avoid the use of strong CYP3A4 inducers and inhibitors. CYP3A sensitive substrates, PgP, BCRP inhibitors
• Have had prior treatment with a TTK/MPS1 inhibitor.
• Part B only: Concomitant active malignancy other than ER+/HER2- advanced breast cancer.
• Part A only: Concomitant active malignancy other than primary malignancy
• Part B only: Had prior treatment with fulvestrant or agents with similar MoA

Other illness

• Have active, acute, or clinically significant chronic infections.
• Primary central nervous system malignancies or known central nervous system metastasis.
• Coagulopathy or any history of coagulopathy within the past 6 months, including history of deep vein thrombosis or pulmonary embolism.
• Part B only: Known bleeding disorder which would prohibit administration of fulvestrant.

Lab values

• 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.

Other

• Are pregnant or nursing.

• 1\. Have histological or cytological proof of advanced cancer that has progressed on at least 1 prior line of systemic therapy
• Breast cancer patients positive for estrogen receptor and/or progesterone receptor and negative for HER2
• Must have previously received a CDK4/6 inhibitor
• No limit on lines of endocrine therapy
• Must have received no more than 1 line of cytotoxic chemotherapy
• Have measurable disease as per RECIST 1.1 guidelines.
• Breast cancer patients positive for estrogen receptor and/or progesterone receptor and negative for HER2
• Must have previously received a CDK4/6 inhibitor
• Must have previously received no more than 1 line of endocrine therapy
• Must have received no more than 1 line of cytotoxic chemotherapy
• Have measurable disease as per RECIST 1.1 guidelines.