A Phase 2 Study of PCS6422 with Capecitabine in Patients with Advanced or Metastatic Breast Cancer

Eligibility Criteria

• 1. Aged ≥18 years at Screening
• 2. Diagnosis of histologically confirmed breast cancer that is unresectable. The following subsets of breast cancer are included:
• 1. Patients with triple-negative breast cancer, advanced or metastatic
• 2. Patients with hormone receptor (HR) positive, ER positive, HER2 negative advanced or metastatic breast cancer
• 3. Has measurable disease in accordance with RECIST 1.1 obtained by imaging within 28 days prior to C1D1
• 4. Other therapies are not indicated (eg, resistant or intolerant to taxanes and/or an anthracycline-containing regimen) for treatment of advanced or metastatic breast cancer
• 5. Has a life expectance of at least 24 weeks
• 6. Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1 at screening
• 7. Has adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days before C1D1 (Note: labs will also be repeated pre-dose on C1D1 to confirm eligibility): a. Hemoglobin ≥9 g/dL (≥90 g/L) b. Adequate renal function by estimated glomerular filtration rate (eGFR) defined as a creatinine clearance \>50 mL/min (\>0.84 mL/s) (Cockcroft-Gault equation) and normalized to body surface area c. Peripheral absolute neutrophil count (ANC) of ≥1.5×109/L d. Platelet count of ≥100×109/L without growth factor/transfusion e. Total bilirubin \<1.5× upper limit of normal (ULN); or ≤3×ULN if the patient has Gilbert's disease f. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \<2.5×ULN, with liver metastasis \<5×ULN g. International normalized ratio (INR) \<1.5 and prothrombin time (PT) ≤1.5×ULN, unless both of the following conditions are met: i. Patient is receiving anticoagulant therapy, and ii. PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulant h. Activated partial thromboplastin time (aPTT) ≤1.5×ULN, unless both of the following conditions are met: i. Patient is receiving anticoagulant therapy, and ii. PT or PTT is within therapeutic range of intended use of anticoagulants
• 1. Received any line of treatment for advanced or metastatic breast cancer within 21 days or 5 half-lives (whichever is longer) prior to randomization
• 2. Currently receiving any hormone replacement therapy, unless discontinued within 21 days prior to randomization
• 3. Received IV 5-FU or oral 5-FU analog in the 4 weeks prior to C1D1
• 4. Received DPD inhibitor within 4 weeks prior to C1D1
• 5. Has homozygous or compound heterozygous DPYD variants that result in complete or near-complete absence of DPD activity
• 6. Cardiac:
• 1. Has history or presence of clinically significant abnormal 12-lead electrocardiogram (ECG) results, in the Medical Monitor or Investigator's opinion
• 2. Has prolonged QTc (with Fridericia's correction) of \>480 msec performed at Screening
• 3. Has a history of prolonged QTc interval, ventricular tachycardia/fibrillation or significant ventricular arrhythmia, or Torsades de Pointes, or a history of ventricular ablation for arrhythmia
• 4. Has congenital long QT syndrome or a family history of long QT syndrome
• 5. Has other clinically significant cardiac disease including, but not limited to, myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery ≤12 months prior to randomization, congestive heart failure
• * Class II per the New York Heart Association, or history of myocarditis
• 7. Is pregnant or breastfeeding