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Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Metastatic TNBC and Tesetaxel Monotherapy in Patients With HER2 Negative MBC (CONTESSA TRIO)

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ClinicalTrials.gov Identifier: NCT03952325
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : May 24, 2019
Sponsor:
Information provided by (Responsible Party):
Odonate Therapeutics, Inc.

Brief Summary:
CONTESSA TRIO is a 2-cohort, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane. In Cohort 1, approximately 90 patients (with potential expansion to up to 150 patients) with locally advanced or metastatic triple-negative breast cancer (TNBC) 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 dual primary endpoints for Cohort 1 are objective response rate (ORR) and progression-free survival (PFS). In Cohort 2, approximately 40 elderly patients (with potential expansion to up to 60 patients) with HER2 negative locally advanced or metastatic breast cancer (MBC) who have not received prior chemotherapy for advanced disease will receive tesetaxel monotherapy. The primary endpoint for Cohort 2 is ORR.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Tesetaxel Drug: Nivolumab Drug: Pembrolizumab Drug: Atezolizumab Phase 2

Detailed Description:

CONTESSA TRIO is a 2-cohort, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane.

Cohort 1:

Approximately 90 patients (with potential expansion to up to 150 patients) with locally advanced or metastatic TNBC 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 (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are immuno-oncology (IO) agents approved for the treatment of multiple types of cancer. One of these agents, atezolizumab, in combination with the intravenously delivered taxane, nab-paclitaxel, was recently approved by the U.S. Food and Drug Administration (FDA) as a first-line treatment for patients with metastatic TNBC. Patients with central nervous system (CNS) metastases are eligible. The dual primary endpoints for Cohort 1 are ORR and PFS. Secondary endpoints include duration of response (DoR) and overall survival (OS).

Cohort 2:

Approximately 40 elderly patients (with potential expansion to up to 60 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. Patients with CNS metastases are eligible. The primary endpoint for Cohort 2 is ORR. Secondary endpoints include PFS, DoR and OS.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Phase 2 Study of Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Metastatic TNBC and Tesetaxel Monotherapy in Elderly Patients With HER2 Negative MBC
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1, Arm A: Tesetaxel plus nivolumab Drug: Tesetaxel
Tesetaxel at 27 mg/m2 orally Q3W

Drug: Nivolumab
Nivolumab at 360 mg by intravenous infusion Q3W

Experimental: Cohort 1, Arm B: Tesetaxel plus pembrolizumab Drug: Tesetaxel
Tesetaxel at 27 mg/m2 orally Q3W

Drug: Pembrolizumab
Pembrolizumab at 200 mg by intravenous infusion Q3W

Experimental: Cohort 1, Arm C: Tesetaxel plus atezolizumab Drug: Tesetaxel
Tesetaxel at 27 mg/m2 orally Q3W

Drug: Atezolizumab
Atezolizumab at 1,200 mg by intravenous infusion Q3W

Experimental: Cohort 2: Tesetaxel Drug: Tesetaxel
Tesetaxel at 27 mg/m2 orally Q3W




Primary Outcome Measures :
  1. Cohort 1: ORR [ Time Frame: Approximately 2.0-3.0 years ]
  2. Cohort 1: PFS [ Time Frame: Approximately 2.5-3.5 years ]
  3. Cohort 2: ORR [ Time Frame: Approximately 2.0-3.0 years ]

Secondary Outcome Measures :
  1. Cohort 1: DoR [ Time Frame: Approximately 2.5-3.5 years ]
  2. Cohort 1: OS [ Time Frame: Approximately 4.0-5.0 years ]
  3. Cohort 2: PFS [ Time Frame: Approximately 2.5-3.5 years ]
  4. Cohort 2: DoR [ Time Frame: Approximately 2.5-3.5 years ]
  5. Cohort 2: OS [ Time Frame: Approximately 4.0-5.0 years ]

Other Outcome Measures:
  1. Cohort 1: ORR by PD-L1 expression [ Time Frame: Approximately 2.0-3.0 years ]
  2. Cohort 1: PFS by PD-L1 expression [ Time Frame: Approximately 2.5-3.5 years ]
  3. Cohort 1: CNS ORR in patients with CNS metastases at baseline [ Time Frame: Approximately 2.0-3.0 years ]
  4. Cohort 1: CNS DoR in patients with CNS metastases at baseline [ Time Frame: Approximately 2.5-3.5 years ]
  5. Cohort 2: ORR by receptor subtype for the hormone receptor (HR) positive and triple-negative subgroups [ Time Frame: Approximately 2.0-3.0 years ]
  6. Cohort 2: CNS ORR in patients with CNS metastases at baseline [ Time Frame: Approximately 2.0-3.0 years ]
  7. Cohort 2: CNS DoR in patients with CNS metastases at baseline [ Time Frame: Approximately 2.5-3.5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female or male patients aged:

    • Cohort 1: ≥ 18 years old
    • Cohort 2: ≥ 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
  • Cohort 2 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: For central determination of PD-L1 expression, adequate, newly obtained or archival core of excisional biopsy
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03952325


Contacts
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Contact: Jen Schroeder 860-389-7921 jschroeder@odonate.com
Contact: Kate McGovren 269-599-1005 kmcgovren@odonate.com

Locations
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United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
New York Cancer and Blood Specialists Recruiting
East Setauket, New York, United States, 11733
Sponsors and Collaborators
Odonate Therapeutics, Inc.
Investigators
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Study Director: Joseph O'Connell, M.D. Odonate Therapeutics, Inc.

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Responsible Party: Odonate Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03952325     History of Changes
Other Study ID Numbers: ODO-TE-B202
First Posted: May 16, 2019    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Odonate Therapeutics, Inc.:
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
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Nivolumab
Pembrolizumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents