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 :
Terminated
(The Sponsor has discontinued the development of tesetaxel)
First Posted : May 16, 2019
Last Update Posted : July 30, 2021
|
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Breast Cancer | Drug: Tesetaxel Drug: Nivolumab Drug: Pembrolizumab Drug: Atezolizumab | Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 294 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 |
Actual Primary Completion Date : | June 23, 2021 |
Actual Study Completion Date : | June 23, 2021 |
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 |
- Cohort 1: ORR in patients with PD-L1 positive status [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 1: PFS in patients with PD-L1 positive status [ Time Frame: Approximately 2.5-3.5 years ]
- Cohort 2: ORR in patients with HR-positive, HER2-negative disease [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 2: PFS in patients with HR-positive, HER2-negative disease [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 3: ORR in patients with HR-positive, HER2-negative disease [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 3: PFS in patients with HR-positive, HER2-negative disease [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 1: ORR in all patients [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 1: PFS in all patients [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 1: DoR [ Time Frame: Approximately 2.5-3.5 years ]
- Cohort 1: OS [ Time Frame: Approximately 4.0-5.0 years ]
- Cohort 2: ORR in patients with triple-negative disease [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 2: PFS in patients with triple-negative disease [ Time Frame: Approximately 2.5-3.5 years ]
- Cohort 2: DoR [ Time Frame: Approximately 2.5-3.5 years ]
- Cohort 2: OS [ Time Frame: Approximately 4.0-5.0 years ]
- Cohort 3: ORR in patients with triple-negative disease [ Time Frame: Approximately 1.0-2.0 years ]
- Cohort 3: PFS in patients with triple-negative disease [ Time Frame: Approximately 1.5-2.5 years ]
- Cohort 3: DoR [ Time Frame: Approximately 2.5-3.5 years ]
- Cohort 3: OS [ Time Frame: Approximately 4.0-5.0 years ]
- Cohort 1: ORR by level of PD-L1 expression as determined by central PD-L1 testing [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 1: PFS by level of PD-L1 expression as determined by central PD-L1 testing [ Time Frame: Approximately 2.5-3.5 years ]
- Cohort 1: Central nervous system (CNS) ORR in patients with CNS metastases at baseline [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 1: CNS DoR in patients with CNS metastases at baseline [ Time Frame: Approximately 2.5-3.5 years ]
- Cohort 2: CNS ORR in patients with CNS metastases at baseline [ Time Frame: Approximately 2.0-3.0 years ]
- Cohort 2: CNS DoR in patients with CNS metastases at baseline [ Time Frame: Approximately 2.5-3.5 years ]
- Cohort 3: CNS ORR in patients with CNS metastases at baseline [ Time Frame: Approximately 1.0-2.0 years ]
- Cohort 3: CNS DoR in patients with CNS metastases at baseline [ Time Frame: Approximately 1.5-2.5 years ]
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.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
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
United States, Florida | |
Sarah Cannon Research Institute - Florida Cancer Specialists | |
Fort Myers, Florida, United States, 33901 | |
Florida Cancer Specialists and Research Institute | |
Saint Petersburg, Florida, United States, 33705 | |
Florida Cancer Specialists and Research Institute - Panhandle Region | |
Tallahassee, Florida, United States, 32308 | |
Florida Cancer Specialists and Research Institute | |
West Palm Beach, Florida, United States, 33401 | |
United States, Massachusetts | |
Dana-Farber Cancer Institute | |
Boston, Massachusetts, United States, 02215 | |
United States, New York | |
New York Cancer and Blood Specialists | |
East Setauket, New York, United States, 11733 | |
United States, Tennessee | |
West Cancer Center | |
Germantown, Tennessee, United States, 38138 | |
United States, Texas | |
Texas Oncology - Baylor Charles A. Sammons Cancer Center | |
Dallas, Texas, United States, 75246 | |
United States, Virginia | |
Virginia Oncology Associates | |
Norfolk, Virginia, United States, 23502 | |
Korea, Republic of | |
Asan Medical Center | |
Seoul, Korea, Republic of | |
Singapore | |
John Hopkins Singapore International Medical Centre | |
Singapore, Singapore | |
National Cancer Centre Singapore | |
Singapore, Singapore |
Study Director: | Joseph O'Connell, M.D. | Odonate Therapeutics, Inc. |
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: | July 30, 2021 |
Last Verified: | July 2021 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Pembrolizumab |
Nivolumab Atezolizumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |