Oral Paclitaxel + Encequidar vs IV Paclitaxel in Treatment of HER2 Negative Metastatic Breast Cancer

Prior treatment

• Not recovered to ≤grade 1 toxicity from previous anticancer treatments or previous investigational product (IP) except alopecia
• Relapsed less than 6 months following treatment with a taxane (paclitaxel or docetaxel) as part of anthracycline-based adjuvant chemotherapy or for metastatic disease
• Currently receiving other medications intended for the treatment of their malignancy
• Received other IPs within 14 days or 5 half-lives of the first study dosing day, whichever is longer
• Received biologics or monoclonal antibodies intended for the treatment of their malignancy within 30 days of the first study dosing day
• Received radiation therapy within 2 weeks prior to signing informed consent or radiation therapy is planned within 6 months from the time of signing informed consent
• Taking a medication known to be a moderate or strong cytochrome P450 (CYP) 3A4 inhibitor or inducer or neurokinin-1 receptor antagonist (NK-1) inhibitor within 14 days prior to start of dosing in the study
• Taking a medication known to be a moderate or strong CYP2C8 inhibitor or inducer within 14 days prior to start of dosing in the study
• Taking an oral medication with a narrow therapeutic index known to be a P-glycoprotein (P-gp) substrate within 24 hours prior to start of dosing in the study
• Taking a medication known to be a P-gp inhibitor or inducer within 14 days prior to start of dosing in the study
• Taking a medication known to be an organic anion transporting polypeptide 1B1/3 (OATP1B1/3) inhibitor
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia, chronic pulmonary disease requiring oxygen, known bleeding disorders, or any concomitant illness or social situation that would limit compliance with study requirements

Other illness

• Major surgery to the upper GI tract, inability to take oral medication, or have a history of GI disease or other medical condition that, in the opinion of the Investigator may interfere with oral drug absorption
• History of significant hypersensitivity-type reaction to paclitaxel or Cremophor EL that would contraindicate the use of IV paclitaxel
• Known allergic reaction or intolerance to contrast media
• Documented history of true systemic allergic reaction to 3 or more medications
• Active hepatitis B (as evidenced by being HBsAg positive) or active hepatitis C (HCV-RNA positive) or cirrhosis of the liver
• Known HIV infection

Other

• QTcF interval ≥470 msec at baseline
• Known active central nervous system metastasis, including leptomeningeal involvement
• The Investigator believes that participation in this study would not be acceptable

• Signed written informed consent
• ≥18 years of age
• Histologically or cytologically confirmed HER2 negative breast cancer for whom IV paclitaxel monotherapy has been recommended.
• HER2 negative per American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guideline. Subjects can be estrogen receptor/progesterone receptor (ER/PR) positive or negative per ASCO CAP guideline, but ER/PR and HER2 receptor status must be known.
• Metastatic breast cancer with target lesions measurable by CT scan per RECIST v1.1 criteria confirmed by BICR
• Adequate hematologic status as demonstrated by not requiring granulocyte colony stimulating factor (G CSF) or transfusion support within 30 days prior to randomization to achieve the following at screening:
  • Absolute neutrophil count (ANC) ≥1500/mm3
  • Platelet count ≥100,000/mm3
  • Hemoglobin ≥9 g/dL
• Adequate liver function as demonstrated by:
  • Total bilirubin ≤upper limit of normal (ULN) unless the subject has Gilbert's disease, for which bilirubin must be ≤2.0 × ULN
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 × ULN
• Adequate renal function as demonstrated by estimated glomerular filtration rate (eGFR) ≥60 mL/min
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy at least 6 months, in the judgment of the Investigator
• Female subjects must be postmenopausal (≥12 months without menses) or surgically sterile (ie, by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or must be using effective contraception (ie, non-hormonal intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for 30 days after their last dose of assigned study treatment.
• Women of childbearing potential must have a negative screening serum pregnancy test and urine test within 4 days prior to start of dosing in the study and not be breast feeding.
• Sexually active male subjects must use a barrier method of contraception during the study and agree to continue the use of male contraception for at least 30 days after the last dose of investigational product (IP).