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.
Title
- Brief Title: Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Triple-Negative MBC and Tesetaxel Monotherapy in Patients With HER2-Negative MBC
- Official Title: 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 and Non-Elderly Adult Patients With HER2-Negative, Locally Advanced or Metastatic Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
ODO-TE-B202
- NCT ID:
NCT03952325
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Tesetaxel | | Cohort 1, Arm A: Tesetaxel plus nivolumab |
Tesetaxel | | Cohort 1, Arm B: Tesetaxel plus pembrolizumab |
Tesetaxel | | Cohort 1, Arm C: Tesetaxel plus atezolizumab |
Nivolumab | | Cohort 1, Arm A: Tesetaxel plus nivolumab |
Pembrolizumab | | Cohort 1, Arm B: Tesetaxel plus pembrolizumab |
Atezolizumab | | Cohort 1, Arm C: Tesetaxel plus atezolizumab |
Tesetaxel | | Cohort 2: Tesetaxel |
Purpose
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.
Detailed 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Cohort 1, Arm A: Tesetaxel plus nivolumab | Experimental | | |
Cohort 1, Arm B: Tesetaxel plus pembrolizumab | Experimental | | |
Cohort 1, Arm C: Tesetaxel plus atezolizumab | Experimental | | |
Cohort 2: Tesetaxel | Experimental | | |
Cohort 3: Tesetaxel | Experimental | | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Cohort 1: ORR in patients with PD-L1 positive status |
Time Frame: | Approximately 2.0-3.0 years |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Cohort 1: ORR in all patients |
Time Frame: | Approximately 2.0-3.0 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 1: PFS in all patients |
Time Frame: | Approximately 2.0-3.0 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 1: DoR |
Time Frame: | Approximately 2.5-3.5 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 1: OS |
Time Frame: | Approximately 4.0-5.0 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 2: ORR in patients with triple-negative disease |
Time Frame: | Approximately 2.0-3.0 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 2: PFS in patients with triple-negative disease |
Time Frame: | Approximately 2.5-3.5 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 2: DoR |
Time Frame: | Approximately 2.5-3.5 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 2: OS |
Time Frame: | Approximately 4.0-5.0 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 3: ORR in patients with triple-negative disease |
Time Frame: | Approximately 1.0-2.0 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 3: PFS in patients with triple-negative disease |
Time Frame: | Approximately 1.5-2.5 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 3: DoR |
Time Frame: | Approximately 2.5-3.5 years |
Safety Issue: | |
Description: | |
Measure: | Cohort 3: OS |
Time Frame: | Approximately 4.0-5.0 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Odonate Therapeutics, Inc. |
Trial Keywords
- Tesetaxel
- PD-(L)1 inhibitor
- Triple-negative breast cancer
- Locally advanced or metastatic breast cancer
- Taxane
- Metastatic breast cancer
- Breast cancer
- Combination of tesetaxel and PD-(L)1 inhibitors
- HER2 negative
- Oral chemotherapy
- Central nervous system (CNS) metastases
Last Updated
July 30, 2021