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)

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tesetaxel; Drug: Nivolumab; Drug: Pembrolizumab; Drug: Atezolizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 294
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Asan Medical Center
• Singapore
  • Singapore, Singapore
    • National Cancer Centre Singapore
  • Singapore, Singapore
    • John Hopkins Singapore International Medical Centre
• United States
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Sarah Cannon Research Institute - Florida Cancer Specialists
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists and Research Institute
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists and Research Institute - Panhandle Region
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists and Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • New York
    • East Setauket, New York, United States, 11733
      • New York Cancer and Blood Specialists
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • West Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Cohort 2: PFS in patients with triple-negative disease	Approximately 2.5-3.5 years
Cohort 2: DoR	Approximately 2.5-3.5 years
Cohort 2: OS	Approximately 4.0-5.0 years
Cohort 3: ORR in patients with triple-negative disease	Approximately 1.0-2.0 years
Cohort 3: PFS in patients with triple-negative disease	Approximately 1.5-2.5 years
Cohort 3: DoR	Approximately 2.5-3.5 years
Cohort 3: OS	Approximately 4.0-5.0 years

Other Outcome Measures

Outcome Measure	Time Frame
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
Cohort 1: CNS DoR in patients with CNS metastases at baseline	Approximately 2.5-3.5 years
Cohort 2: CNS ORR in patients with CNS metastases at baseline	Approximately 2.0-3.0 years
Cohort 2: CNS DoR in patients with CNS metastases at baseline	Approximately 2.5-3.5 years
Cohort 3: CNS ORR in patients with CNS metastases at baseline	Approximately 1.0-2.0 years
Cohort 3: CNS DoR in patients with CNS metastases at baseline	Approximately 1.5-2.5 years

Collaborators and Investigators

• Sponsor: Odonate Therapeutics, Inc.
• Investigators: Study Director: Joseph O'Connell, M.D., Odonate Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2019
• Primary Completion (Actual): June 23, 2021
• Study Completion (Actual): June 23, 2021

Study Registration Dates

• First Submitted: May 14, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (Actual): May 16, 2019

Study Record Updates

• Last Update Posted (Actual): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Breast cancer; HER2 negative; Metastatic breast cancer; Triple-negative breast cancer; Tesetaxel; Taxane; Locally advanced or metastatic breast cancer; Central nervous system (CNS) metastases; Oral chemotherapy; PD-(L)1 inhibitor; Combination of tesetaxel and PD-(L)1 inhibitors
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Pembrolizumab; Atezolizumab
• Other Study ID Numbers: ODO-TE-B202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No