A Multinational, 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

Protocol # :
Breast Cancer
Disease Sites
Principal Investigator
Tolaney, Sara, M
Site Investigator
Patel, Jaymin
Site Research Nurses
Agius, Christine
Bowers, Danielle, Marie
Campbell, Margaret
Caradonna, Lisa
Czapla, Lauren
Hershey, Allie
Hill, Brittany, Danielle
Kasparian, Elizabeth
McKenna, Jennifer
O'Neil, Kelly
O'Reilly, Elizabeth
Ritzer, Jolivette, Chong
Rutter, Morgan
Salehi, Elahe
Shaw, Lindsay, Hamilton
Tamargo, Ryan, S.
Turgeon, Margaret

Trial Description

CONTESSA 2 is a multinational, multicenter, Phase 2 study of tesetaxel in patients with
HER2 negative, HR positive, locally advanced or metastatic breast cancer (LA/MBC) not
previously treated with a taxane. The primary objective of the study is to establish the
efficacy of tesetaxel plus a reduced dose of capecitabine based on objective response
rate (ORR) as assessed by an Independent Radiologic Review Committee (IRC). 152 patients
were enrolled.

Eligibility Requirements

Inclusion criteria:

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

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

- 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

- 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

- 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

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

Exclusion criteria:

1. Two or more prior chemotherapy regimens for advanced disease

2. Prior treatment with a taxane at any dose

3. Prior treatment with capecitabine at any dose

4. Current evidence of leptomeningeal disease

5. Other cancer that required therapy within the preceding 5 years other than
adequately treated: (a) non-melanoma skin cancer or in situ cancer; or (b) following
approval by the Medical Monitor, other cancer that has a very low risk of
interfering with the safety or efficacy endpoints of the Study

6. Known human immunodeficiency virus infection, unless well controlled. Patients who
are on an adequate antiviral regimen with no evidence of active infection are
considered well controlled.

7. Active hepatitis B or active hepatitis C infection

8. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with Study participation or
investigational product administration or may interfere with the interpretation of
Study results and, in the judgment of the Investigator, would make the patient
inappropriate for entry into this Study.

9. Presence of neuropathy > Grade 1 per NCI CTCAE version 5.0

10. Anticancer treatment, including endocrine therapy, radiotherapy (except stereotactic
brain radiosurgery), chemotherapy, biologic therapy, or therapy in an
investigational clinical study, ≤ 14 days prior to the date of Enrollment

11. Major surgery ≤ 28 days prior to the date of Enrollment; patient must have complete
recovery from surgery

12. Less than 2 weeks or 5 plasma half-lives (whichever is greater) since last use of a
medication or ingestion of an agent, beverage, or food that is a known clinically
relevant strong inhibitor or known clinically relevant inducer of the cytochrome
P450 (CYP)3A pathway (patients should discontinue taking any regularly-taken
medication that is a strong inhibitor or inducer of the CYP3A pathway)

13. History of hypersensitivity or unexpected reactions to capecitabine,
fluoropyrimidine agents or any of their ingredients

14. Known dihydropyrimidine dehydrogenase (DPD) deficiency. Testing for DPD deficiency
must be performed where required by local regulations, using a validated method that
is approved by local health authorities.

15. Pregnant or breastfeeding

16. If, in the opinion of the Investigator, the patient is deemed unwilling or unable to
comply with the requirements of the Study

17. Treatment with brivudine, sorivudine, or its chemically-related analogs ≤ 28 days
prior to the date of Enrollment