Breast Cancer Clinical Trial
Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Triple-Negative MBC and Tesetaxel Monotherapy in Patients With HER2-Negative MBC
Summary
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.
Full Description
CONTESSA TRIO is a multi-cohort, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with MBC.
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 dosed orally at 27 mg/m2 once every three weeks (Q3W) plus either:
Nivolumab at 360 mg by intravenous infusion Q3W;
Pembrolizumab at 200 mg by intravenous infusion Q3W; or
Atezolizumab at 1,200 mg by intravenous infusion Q3W.
Nivolumab and pembrolizumab (programmed cell death protein 1 [PD-1] inhibitors) and atezolizumab (a programmed death-ligand 1 [PD-L1] inhibitor) are immuno-oncology (IO) agents approved for the treatment of multiple types of cancer. Two of these agents, atezolizumab and pembrolizumab, have been approved by the U.S. Food and Drug Administration (FDA) as a first-line treatment for patients with triple-negative MBC. The primary efficacy endpoints for Cohort 1 are ORR and PFS in patients with PD-L1 positive status. The secondary efficacy endpoints are ORR and PFS in all patients, duration of response (DoR) and overall survival (OS).
Cohort 2:
Approximately 60 elderly patients with HER2-negative MBC who have not received prior chemotherapy for advanced disease will receive tesetaxel monotherapy dosed orally at 27 mg/m2 Q3W. The primary efficacy endpoints for Cohort 2 are ORR and PFS in patients with HR-positive, HER2-negative disease. The secondary efficacy endpoints are ORR and PFS in patients with triple-negative disease, DoR and OS.
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 dosed orally at 27 mg/m2 Q3W. The primary efficacy endpoints for Cohort 3 are ORR and PFS in patients with HR positive, HER2-negative disease. The secondary efficacy endpoints are ORR and PFS in patients with triple negative disease, DoR and OS.
Eligibility Criteria
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 therapies.
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) inhibitor
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 applicable
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
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There are 9 Locations for this study
Fort Myers Florida, 33901, United States
Saint Petersburg Florida, 33705, United States
Tallahassee Florida, 32308, United States
West Palm Beach Florida, 33401, United States
Boston Massachusetts, 02215, United States
East Setauket New York, 11733, United States
Germantown Tennessee, 38138, United States
Dallas Texas, 75246, United States
Norfolk Virginia, 23502, United States
Seoul , , Korea, Republic of
Singapore , , Singapore
Singapore , , Singapore
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