Clinical Trials /

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

NCT03952325

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Metastatic TNBC and Tesetaxel Monotherapy in Patients With HER2 Negative MBC
  • 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

Clinical Trial IDs

  • ORG STUDY ID: ODO-TE-B202
  • NCT ID: NCT03952325

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
TesetaxelCohort 1, Arm A: Tesetaxel plus nivolumab
TesetaxelCohort 1, Arm B: Tesetaxel plus pembrolizumab
TesetaxelCohort 1, Arm C: Tesetaxel plus atezolizumab
NivolumabCohort 1, Arm A: Tesetaxel plus nivolumab
PembrolizumabCohort 1, Arm B: Tesetaxel plus pembrolizumab
AtezolizumabCohort 1, Arm C: Tesetaxel plus atezolizumab
TesetaxelCohort 2: Tesetaxel

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1, Arm A: Tesetaxel plus nivolumabExperimental
  • Tesetaxel
  • Nivolumab
Cohort 1, Arm B: Tesetaxel plus pembrolizumabExperimental
  • Tesetaxel
  • Pembrolizumab
Cohort 1, Arm C: Tesetaxel plus atezolizumabExperimental
  • Tesetaxel
  • Atezolizumab
Cohort 2: TesetaxelExperimental
  • Tesetaxel

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Cohort 1: ORR
Time Frame:Approximately 2.0-3.0 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Cohort 1: DoR
Time Frame:Approximately 2.5-3.5 years
Safety Issue:
Description:
Measure:Cohort 1: OS
Time Frame:Approximately 4.0-5.0 years
Safety Issue:
Description:
Measure:Cohort 2: PFS
Time Frame:Approximately 2.5-3.5 years
Safety Issue:
Description:
Measure:Cohort 2: DoR
Time Frame:Approximately 2.5-3.5 years
Safety Issue:
Description:
Measure:Cohort 2: OS
Time Frame:Approximately 4.0-5.0 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Odonate Therapeutics, Inc.

Trial 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

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