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

Inclusion Criteria: Part A Escalation

1. Have histological or cytological proof of advanced cancer that has progressed on atleast 1 prior line of systemic therapy

Inclusion Criteria: Part A Expansion

1. Breast cancer patients positive for estrogen receptor and/or progesterone receptorand negative for HER2

2. Must have previously received a CDK4/6 inhibitor

3. No limit on lines of endocrine therapy

4. Must have received no more than 1 line of cytotoxic chemotherapy

5. Have measurable disease as per RECIST 1.1 guidelines.

Inclusion Criteria: Part B

1. Breast cancer patients positive for estrogen receptor and/or progesterone receptorand negative for HER2

2. Must have previously received a CDK4/6 inhibitor

3. Must have previously received no more than 1 line of endocrine therapy

4. Must have received no more than 1 line of cytotoxic chemotherapy

5. Have measurable disease as per RECIST 1.1 guidelines.

Exclusion Criteria: All Parts

1. Are pregnant or nursing.

2. Have received chemotherapy, biological therapy, or investigational treatment lessthan 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of studydrug. Have received radiotherapy less than 2 weeks prior to first dose of studydrug.

3. Received growth factors within 14 days prior to initiation of dosing of CFI-402257or 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 systemmetastasis.

8. Being treated with full dose warfarin.

9. Coagulopathy or any history of coagulopathy within the past 6 months, includinghistory of deep vein thrombosis or pulmonary embolism.

10. Patients must avoid the use of strong CYP3A4 inducers and inhibitors. CYP3Asensitive substrates, PgP, BCRP inhibitors

11. Have had prior treatment with a TTK/MPS1 inhibitor.

12. Part B only: Known bleeding disorder which would prohibit administration offulvestrant.

13. Part B only: Concomitant active malignancy other than ER+/HER2- advanced breastcancer.

14. Part A only: Concomitant active malignancy other than primary malignancy

15. Part B only: Had prior treatment with fulvestrant or agents with similar MoA