Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Triple-Negative MBC and Tesetaxel Monotherapy in Patients With HER2-Negative MBC

NCT03952325 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: ODO-TE-B202
• Study Type: interventional
• Target: 294
• Locations: 3 countries
• Sites: 12

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.

Conditions

Breast Cancer

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

Outcome Measures

Primary Outcomes (6)

• Cohort 1: ORR in patients with PD-L1 positive status

  Approximately 2.0-3.0 years

• Cohort 1: PFS in patients with PD-L1 positive status

  Approximately 2.5-3.5 years

• Cohort 2: ORR in patients with HR-positive, HER2-negative disease

  Approximately 2.0-3.0 years

• Cohort 2: PFS in patients with HR-positive, HER2-negative disease

  Approximately 2.0-3.0 years

• Cohort 3: ORR in patients with HR-positive, HER2-negative disease

  Approximately 2.0-3.0 years

• Cohort 3: PFS in patients with HR-positive, HER2-negative disease

  Approximately 2.0-3.0 years

Secondary Outcomes (12)

• Cohort 1: ORR in all patients

  Approximately 2.0-3.0 years

• Cohort 1: PFS in all patients

  Approximately 2.0-3.0 years

• Cohort 1: DoR

  Approximately 2.5-3.5 years

• Cohort 1: OS

  Approximately 4.0-5.0 years

• Cohort 2: ORR in patients with triple-negative disease

  Approximately 2.0-3.0 years

Other Outcomes (8)

• Cohort 1: ORR by level of PD-L1 expression as determined by central PD-L1 testing

  Approximately 2.0-3.0 years

• Cohort 1: PFS by level of PD-L1 expression as determined by central PD-L1 testing

  Approximately 2.5-3.5 years

• Cohort 1: Central nervous system (CNS) ORR in patients with CNS metastases at baseline

  Approximately 2.0-3.0 years

Study Arms (5)

Cohort 1, Arm A: Tesetaxel plus nivolumab

EXPERIMENTAL

Drug: Tesetaxel; Drug: Nivolumab

Cohort 1, Arm B: Tesetaxel plus pembrolizumab

EXPERIMENTAL

Drug: Tesetaxel; Drug: Pembrolizumab

Cohort 1, Arm C: Tesetaxel plus atezolizumab

EXPERIMENTAL

Drug: Tesetaxel; Drug: Atezolizumab

Cohort 2: Tesetaxel

EXPERIMENTAL

Drug: Tesetaxel

Cohort 3: Tesetaxel

EXPERIMENTAL

Drug: Tesetaxel

Interventions

Tesetaxel DRUG

Tesetaxel at 27 mg/m2 orally Q3W

Cohort 1, Arm A: Tesetaxel plus nivolumab

Nivolumab DRUG

Nivolumab at 360 mg by intravenous infusion Q3W

Cohort 1, Arm A: Tesetaxel plus nivolumab

Pembrolizumab DRUG

Pembrolizumab at 200 mg by intravenous infusion Q3W

Cohort 1, Arm B: Tesetaxel plus pembrolizumab

Atezolizumab DRUG

Atezolizumab at 1,200 mg by intravenous infusion Q3W

Cohort 1, Arm C: Tesetaxel plus atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Odonate Therapeutics, Inc.: lead

Study Sites (12)

Sarah Cannon Research Institute - Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Specialists and Research Institute

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists and Research Institute - Panhandle Region

Tallahassee, Florida, 32308, United States

Location

Florida Cancer Specialists and Research Institute

West Palm Beach, Florida, 33401, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

New York Cancer and Blood Specialists

East Setauket, New York, 11733, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

John Hopkins Singapore International Medical Centre

Singapore, Singapore

Location

National Cancer Centre Singapore

Singapore, Singapore

Location

Asan Medical Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms; Neoplasm Metastasis

Interventions

tesetaxel; Nivolumab; pembrolizumab; atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Joseph O'Connell, M.D.

  Odonate Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 16, 2019
• Study Start: July 9, 2019
• Primary Completion: June 23, 2021
• Study Completion: June 23, 2021
• Last Updated: July 30, 2021

Record last verified: 2021-07

Locations

US (9); KR (1); SG (2)