A Phase I Study of CX5461

Inclusion Criteria

• •\- Tumour Type Phase I Escalation: Patients must have histologically/and or cytologically confirmed solid malignancy that is advanced/metastatic/recurrent or unresectable and for which no curative therapy exists.
• •Phase I Expansion: Patients must have metastatic/recurrent/locally advanced/unresectable breast cancer with known BRCA1/2 or HRD germline aberrations.
• •All patients must have a formalin fixed paraffin embedded tissue block (from primary or metastatic tumour) available and must have provided informed consent for the release of the block. All patients must also have provided informed consent for a whole blood sample (after implementation of amendment 3).
• •All patients enrolled after the implementation of Amendment 2 must also have provided informed consent for, and be willing to undergo, a skin biopsy (of an area including hair follicles, that is not sun-exposed) prior to treatment (after registration) and after cycle 1 day 15 (C1D16). Paired tumour biopsies will also be required for 6-8 patients enrolled to the RP2D expansion. Note: During accrual to this portion of the study, it may be necessary to restrict accrual to patients who are suitable for, and have consented to, tumour and skin biopsies. Paired tumour biopsies are strongly recommended for all patients
• •Patients must be ≥ 18 years of age.
• •Patients must have an ECOG performance status of 0, 1, or 2.
• •Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to registration (within 35 days if negative).
• •* Phase I: patients do not need to have measurable disease
• •* Phase I Expansion: patients must have measurable disease
• •Previous Therapy
• •Cytotoxic Chemotherapy:
• •Phase I: There is no limit to the number of prior regimens received.
• •Phase I Expansion: Patients must have received at least one but no more than 3 regimens for advanced disease (Note: adjuvant anthracycline/taxane containing chemotherapy is considered an advanced regimen) Note: initially, there is no limitation to the use of prior platinumor PARPi containing regimens. During the expansion accrual may be limited to patients considered to be platinum naive, or platinum sensitive (no evidence of disease progression on or within 3 months of the last dose) or PARPi naïve or exposed. Sites will be informed at the time of the opening of the cohorts
• •Other Systemic Therapy:
• •There is no limit to the number of prior therapies.
• •Patients must have recovered (to baseline or ≤ grade 1) from all reversible toxicity related to prior chemotherapy or systemic therapy and have adequate washout as follows:
• •Longest of one of the following:
• •Two weeks,
• •5 half-lives for investigational agents,
• •Standard cycle length of standard therapies.
• •Radiation:
• •Prior external beam radiation is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose of radiation and date of registration. Exceptions may be made for low-dose, non-myelosuppressive radiotherapy after consultation with CCTG. Concurrent radiotherapy is not permitted.
• •Surgery:
• •Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have elapsed between any major surgery and date of registration, and that wound healing has occurred.
• •Lab Requirements Absolute neutrophils: ≥ 1.5 x 10\^9/L Platelets: ≥ 100 x 10\^9/L Bilirubin: ≤ 1.5 x ULN (upper limit of normal) AST/ALT: ≤ 2.5 x ULN ≤ 5.0 x ULN if patient has liver metastases Serum creatinine: ≤ 1.25 x ULN Creatinine clearance: ≥ 50 mL/min
• •Women/men of childbearing potential must have agreed to use two effective contraceptive methods while on study and for 6 months after the last dose of CX5461.
• •Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
• •Patients must be accessible for treatment and follow up.
• •Treatment is to begin within 2 working days of patient registration.