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Trial record 5 of 5 for:    tesetaxel | Breast Cancer

Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Triple-Negative MBC 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 : January 15, 2021
Sponsor:
Information provided by (Responsible Party):
Odonate Therapeutics, Inc.

Brief 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.

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

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 320 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 9, 2019
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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

Experimental: Cohort 3: Tesetaxel Drug: Tesetaxel
Tesetaxel at 27 mg/m2 orally Q3W




Primary Outcome Measures :
  1. Cohort 1: ORR in patients with PD-L1 positive status [ Time Frame: Approximately 2.0-3.0 years ]
  2. Cohort 1: PFS in patients with PD-L1 positive status [ Time Frame: Approximately 2.5-3.5 years ]
  3. Cohort 2: ORR in patients with HR-positive, HER2-negative disease [ Time Frame: Approximately 2.0-3.0 years ]
  4. Cohort 2: PFS in patients with HR-positive, HER2-negative disease [ Time Frame: Approximately 2.0-3.0 years ]
  5. Cohort 3: ORR in patients with HR-positive, HER2-negative disease [ Time Frame: Approximately 2.0-3.0 years ]
  6. Cohort 3: PFS in patients with HR-positive, HER2-negative disease [ Time Frame: Approximately 2.0-3.0 years ]

Secondary Outcome Measures :
  1. Cohort 1: ORR in all patients [ Time Frame: Approximately 2.0-3.0 years ]
  2. Cohort 1: PFS in all patients [ Time Frame: Approximately 2.0-3.0 years ]
  3. Cohort 1: DoR [ Time Frame: Approximately 2.5-3.5 years ]
  4. Cohort 1: OS [ Time Frame: Approximately 4.0-5.0 years ]
  5. Cohort 2: ORR in patients with triple-negative disease [ Time Frame: Approximately 2.0-3.0 years ]
  6. Cohort 2: PFS in patients with triple-negative disease [ Time Frame: Approximately 2.5-3.5 years ]
  7. Cohort 2: DoR [ Time Frame: Approximately 2.5-3.5 years ]
  8. Cohort 2: OS [ Time Frame: Approximately 4.0-5.0 years ]
  9. Cohort 3: ORR in patients with triple-negative disease [ Time Frame: Approximately 1.0-2.0 years ]
  10. Cohort 3: PFS in patients with triple-negative disease [ Time Frame: Approximately 1.5-2.5 years ]
  11. Cohort 3: DoR [ Time Frame: Approximately 2.5-3.5 years ]
  12. Cohort 3: OS [ Time Frame: Approximately 4.0-5.0 years ]

Other Outcome Measures:
  1. Cohort 1: ORR by level of PD-L1 expression as determined by central PD-L1 testing [ Time Frame: Approximately 2.0-3.0 years ]
  2. Cohort 1: PFS by level of PD-L1 expression as determined by central PD-L1 testing [ Time Frame: Approximately 2.5-3.5 years ]
  3. Cohort 1: Central nervous system (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: CNS ORR in patients with CNS metastases at baseline [ Time Frame: Approximately 2.0-3.0 years ]
  6. Cohort 2: CNS DoR in patients with CNS metastases at baseline [ Time Frame: Approximately 2.5-3.5 years ]
  7. Cohort 3: CNS ORR in patients with CNS metastases at baseline [ Time Frame: Approximately 1.0-2.0 years ]
  8. Cohort 3: CNS DoR in patients with CNS metastases at baseline [ Time Frame: Approximately 1.5-2.5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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
    • 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

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: Stew Kroll 650-576-9679 skroll@odonate.com

Locations
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United States, Florida
Sarah Cannon Research Institute - Florida Cancer Specialists Recruiting
Fort Myers, Florida, United States, 33901
Florida Cancer Specialists and Research Institute Recruiting
Saint Petersburg, Florida, United States, 33705
Florida Cancer Specialists and Research Institute - Panhandle Region Recruiting
Tallahassee, Florida, United States, 32308
Florida Cancer Specialists and Research Institute Recruiting
West Palm Beach, Florida, United States, 33401
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
United States, Tennessee
West Cancer Center Recruiting
Germantown, Tennessee, United States, 38138
United States, Texas
Texas Oncology - Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
United States, Virginia
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of
Singapore
John Hopkins Singapore International Medical Centre Recruiting
Singapore, Singapore
National Cancer Centre Singapore Recruiting
Singapore, Singapore
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    
Other Study ID Numbers: ODO-TE-B202
First Posted: May 16, 2019    Key Record Dates
Last Update Posted: January 15, 2021
Last Verified: January 2021

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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
Triple-negative breast cancer
Locally advanced or metastatic breast cancer
Metastatic breast cancer
Breast cancer
Combination of tesetaxel and PD-(L)1 inhibitors
PD-(L)1 inhibitor
Taxane
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
Pembrolizumab
Nivolumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents