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

This is an adaptive Phase 2, open-label, randomized, multi-center study evaluating up to 2 regimens of PCS6422 with Cap vs. standard dose of Cap alone in patients with advanced or metastatic breast cancer who are not eligible for anthracycline- or taxane-containing therapies, or other available therapies, including PD-1 or PARP inhibitors. The goal of the study is to assess the efficacy and safety of PCS6422 + Cap as a treatment option for patients with advanced or metastatic breast cancer who have been treated with chemotherapy in the metastatic setting.

Inclusion criteria

• Aged ≥18 years at Screening
• Diagnosis of histologically confirmed breast cancer that is unresectable. The following subsets of breast cancer are included:

• Patients with triple-negative breast cancer, advanced or metastatic
• Patients with hormone receptor (HR) positive, ER positive, HER2 negative advanced or metastatic breast cancer
• Has measurable disease in accordance with RECIST 1.1 obtained by imaging within 28 days prior to C1D1
• 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
• Has a life expectance of at least 24 weeks
• Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1 at screening
• 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

Exclusion criteria

• Received any line of treatment for advanced or metastatic breast cancer within 21 days or 5 half-lives (whichever is longer) prior to randomization
• Currently receiving any hormone replacement therapy, unless discontinued within 21 days prior to randomization
• Received IV 5-FU or oral 5-FU analog in the 4 weeks prior to C1D1
• Received DPD inhibitor within 4 weeks prior to C1D1
• Has homozygous or compound heterozygous DPYD variants that result in complete or near-complete absence of DPD activity
• Cardiac:

• Has history or presence of clinically significant abnormal 12-lead electrocardiogram (ECG) results, in the Medical Monitor or Investigator's opinion
• Has prolonged QTc (with Fridericia's correction) of >480 msec performed at Screening
• 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
• Has congenital long QT syndrome or a family history of long QT syndrome
• 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
• Is pregnant or breastfeeding