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

Sponsor

Odonate Therapeutics, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT03952325

Collaborator

(none)

294

Enrollment

Locations

Arms

23.5

Actual Duration (Months)

24.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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: Tesetaxel Drug: Tesetaxel Drug: Nivolumab Drug: Pembrolizumab Drug: Atezolizumab Drug: Tesetaxel	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.

Study Design

Study Type:

Interventional

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 :

Jul 9, 2019

Actual Primary Completion Date :

Jun 23, 2021

Actual Study Completion Date :

Jun 23, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sarah Cannon Research Institute - Florida Cancer Specialists	Fort Myers	Florida	United States	33901
2	Florida Cancer Specialists and Research Institute	Saint Petersburg	Florida	United States	33705
3	Florida Cancer Specialists and Research Institute - Panhandle Region	Tallahassee	Florida	United States	32308
4	Florida Cancer Specialists and Research Institute	West Palm Beach	Florida	United States	33401
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	New York Cancer and Blood Specialists	East Setauket	New York	United States	11733
7	West Cancer Center	Germantown	Tennessee	United States	38138
8	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
9	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
10	Asan Medical Center	Seoul		Korea, Republic of
11	John Hopkins Singapore International Medical Centre	Singapore		Singapore
12	National Cancer Centre Singapore	Singapore		Singapore