CONTESSA 2: This phase II trial is evaluating the effectiveness of two oral chemotherapy drugs (Tesetaxel plus a reduced dose of Capecitabine) in patients with advanced or metastatic breast cancer who have not previously received this type of treatmentMultinational, Multicenter, Phase 2 Study of Tesetaxel Plus a Reduced Dose of Capecitabine in Patients With HER2 Negative, Hormone Receptor Positive, Locally Advanced or Metastatic Breast Cancer Who Have Not Previously Received a Taxane

Inclusion

1. Female or male patients at least 18 years of age
2. Histologically or cytologically confirmed breast cancer
3. HER2 negative disease based on local testing: American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines should be utilized for assessing HER2 status
4. HR (ER and/or PgR) positive disease based on local testing: ASCO/CAP guidelines should be utilized for assessing HR status

5. Measurable disease per RECIST 1.1, including bone-only disease with measurable lytic component.

   Patients with bone-only metastatic cancer must have a measurable lytic or mixed lytic-blastic lesion that can be accurately assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Patients with bone-only disease without a measurable lytic component (ie, blastic-only metastasis) are not eligible.

   Known metastases to the CNS are permitted but not required. The following criteria apply:

   • Patients must be neurologically stable and either off corticosteroids or currently treated with a maximum daily dose of 4 mg of dexamethasone (or equivalent), with no increase in corticosteroid dose within 7 days prior to Enrollment (defined as the time of Sponsor approval of treatment dose)
   • Patients with a history of CNS metastases but with no current evidence of CNS lesions following local therapy are eligible
   • Patients may have CNS metastases that are stable or progressing radiologically
   • Patients with current evidence of leptomeningeal disease are not eligible
   • Patients may have untreated brain metastases or previously treated brain metastases, as long as no immediate local CNS-directed therapy is indicated
   • Any prior whole brain radiation therapy must have been completed > 14 days prior to the date of Enrollment
   • Prior stereotactic brain radiosurgery is permitted
   • CNS surgical resection must have been completed > 28 days prior to the date of Enrollment; patient must have complete recovery from surgery
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
7. Prior endocrine therapy with or without a CDK 4/6 inhibitor unless endocrine therapy is not indicated (ie, short relapse-free interval while on adjuvant endocrine therapy [endocrine resistance]; rapidly progressing disease/visceral crisis; or endocrine intolerance). Any targeted therapies approved for HER2 negative, HR positive LA/MBC, including everolimus, are permitted as prior therapy. There is no limit to the number of prior endocrine therapies.
8. Documented (including de novo): (a) locally advanced breast cancer that is not considered curable by surgery and/or radiation; or (b) metastatic breast cancer

9. Adequate hematologic, hepatic and renal function, as evidenced by:

   • Absolute neutrophil count (ANC) ≥ 1,500/μL without colony-stimulating factor support
   • Platelet count ≥ 100,000/μL
   • Hemoglobin ≥ 10 g/dL without need for hematopoietic growth factor or transfusion support
   • Total bilirubin < 1.5 × upper limit of normal (ULN); does not apply to patients with Gilbert's syndrome
   • Alanine aminotransferase (ALT) < 3 × ULN unless hepatic metastases are present then < 5 × ULN
   • Aspartate aminotransferase (AST) < 3 × ULN unless hepatic metastases are present then < 5 × ULN
   • Alkaline phosphatase < 2.5 × ULN unless hepatic metastases are present then < 5 × ULN
   • Calculated creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula or local standard)
   • Serum albumin ≥ 3.0 g/dL
   • Prothrombin time (PT) < 1.5 × ULN or international normalized ratio (INR) < 1.3 and partial thromboplastin time (PTT) < 1.5 × ULN, unless the patient is on a therapeutic anticoagulant
10. Complete recovery to baseline or Grade 1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 from adverse effects of prior surgery, radiotherapy, endocrine therapy, and other therapy, as applicable, with the exception of Grade 2 alopecia from prior chemotherapy
11. Ability to swallow an oral solid-dosage form of medication
12. A negative serum pregnancy test within 7 days prior to the first dose of Study treatment in women of childbearing potential (ie, all women except those who are post menopause for ≥ 1 year or who have a history of hysterectomy or surgical sterilization)

13. Women of childbearing potential must use an effective, non-hormonal form of contraception from Screening throughout the Treatment Phase and until 70 days after the last dose of Study treatment

    • Acceptable methods include: copper intrauterine device or double barrier methods, including male/female condoms with spermicide and use of contraceptive sponge, cervical cap, or diaphragm

14. Male patients must use an effective, non-hormonal form of contraception from Screening throughout the Treatment Phase and until 130 days after the last dose of Study treatment

    • Acceptable methods include: male/female condoms with spermicide, or vasectomy with medical confirmation of surgical success
15. Written informed consent and authorization to use and disclose health information
16. Ability to comprehend and comply with the requirements of the Study