A Multicenter, Phase 2 Study of Tesetaxel plus Three Different PD-(L)1 Inhibitors in Patients with Triple-Negative, Locally Advanced or Metastatic Breast Cancer and Tesetaxel Monotherapy in Elderly Patients with HER2 Negative, Locally Advanced or Metastatic Breast Cancer

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

Trial Description

CONTESSA TRIO is a multi-cohort, multicenter, Phase 2 study of tesetaxel, an investigational,
orally administered taxane, in patients with metastatic breast cancer (MBC). In Cohort 1,
approximately 200 patients with triple-negative MBC who have not received prior chemotherapy
for advanced disease will be randomized 1:1:1 to receive tesetaxel plus either: (1)
nivolumab; (2) pembrolizumab; or (3) atezolizumab. The primary efficacy endpoints for Cohort
1 are objective response rate (ORR) and progression free survival (PFS) in patients with
programmed death-ligand 1 (PD-L1) positive status. In Cohort 2, approximately 60 elderly
patients with human epidermal growth factor receptor 2 (HER2) negative MBC who have not
received prior chemotherapy for advanced disease will receive tesetaxel monotherapy. The
primary efficacy endpoints for Cohort 2 are ORR and PFS in patients with hormone receptor
(HR)-positive, HER2-negative disease. In Cohort 3, approximately 60 non-elderly adult
patients with HER2-negative MBC who have not received prior chemotherapy for advanced disease
will receive tesetaxel monotherapy. The primary efficacy endpoints for Cohort 3 are ORR and
PFS in patients with HR positive, HER2-negative disease.

Eligibility Requirements

Inclusion Criteria:

- Female or male patients aged:

- Cohort 1: ≥ 18 years old

- Cohort 2: ≥ 65 years old

- Cohort 3: ≥ 18 to < 65 years old

- Histologically or cytologically confirmed breast cancer

- Most recent biopsy must be HER2-negative

- Cohort 1 only: Most recent biopsy must be hormone receptor (HR) (estrogen receptor and
progesterone receptor) negative

- Measurable disease per RECIST 1.1.

- Patients with bone-only metastatic cancer must have a measurable lytic or mixed
lytic-blastic lesion

- Known metastases to the CNS are permitted but not required

- Documented (including de novo): (a) locally advanced breast cancer that is not
considered curable by surgery and/or radiation; or (b) metastatic breast cancer

- Disease-free interval of at least 12 months after the completion of systemic
neoadjuvant or adjuvant chemotherapy for patients previously treated with systemic
chemotherapy for a tumor surgically resected with curative intent

- Cohorts 2 and 3 only: Prior endocrine therapy with or without a cyclin-dependent
kinase (CDK) 4/6 inhibitor unless endocrine therapy is not indicated. Any prior
targeted therapies are permitted. There is no limit to the number of prior endocrine

- Cohort 1 only: At Screening, patients must have documented evidence of positive PD-L1
expression as assessed via immunohistochemistry (IHC) scoring by local, regional, or
central laboratory testing

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

- Adequate bone marrow, hepatic and renal function

Exclusion Criteria:

- Prior chemotherapy for locally advanced or metastatic disease

- Cohort 1 only: prior treatment with pembrolizumab, nivolumab, atezolizumab, any other
PD-(L)1/PD-L2 inhibitor or a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)

- Current evidence or history of leptomeningeal disease

- Known human immunodeficiency virus infection, unless well controlled

- Known active hepatitis B or known active hepatitis C infection

- 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

- Presence of neuropathy Grade > 1

- History of hypersensitivity to any of the Study drugs or any of their ingredients, as

- Cohort 1 only:

- Chronic autoimmune disease

- Evidence of active, non-infectious pneumonia (eg, pneumonia due to autoimmune or
connective tissue disease)

- Treatment with a live vaccine within 30 days prior to the first dose of
nivolumab, pembrolizumab or atezolizumab

- History of active tuberculosis

- Prior organ transplantation including allogeneic stem cell transplantation

- Active infection requiring systemic therapy

- Current or prior use of immunosuppressive medication within 7 days prior to Cycle
1, Day 1

- Active autoimmune disease that might deteriorate when receiving an
immunostimulatory agent

- Anticancer treatment, including endocrine therapy, radiotherapy (except stereotactic
brain radiosurgery), chemotherapy or biologic therapy, ≤ 14 days prior to Enrollment

- Major surgery ≤ 28 days prior to Enrollment

- 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