Breast cancer MedDRA version: 21.1 Level: PT Classification code 10061020 Term: Breast cancer male System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10006201 Term: Breast cancer stage III System Organ Class: 100
Conditions
Sponsors
Odonate Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female or male patients aged: Cohort 1: = 18 years old Cohort 2: = 65 years old 2. Histologically or cytologically confirmed breast cancer 3. Most recent biopsy must be HER2 negative based on local testing: American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines should be utilized for assessing HER2 status 4. Cohort 1 only: Most recent biopsy must be hormone receptor (HR) (estrogen receptor and progesterone receptor) negative based on local testing per ASCO/CAP guidelines 5. Measurable disease per RECIST 1.1. Patients with bone-only metastatic cancer must have a measurable lytic or mixed lytic-blastic lesion that can be accurately assessed by computerized tomography (CT) or magnetic resonance imaging (MRI). Patients with bone-only disease without a lytic component (ie, blastic-only metastasis) are not eligible. Known metastases to the CNS are permitted but not required. The following criteria apply: o Patients must be neurologically stable and off corticosteroids for = 7 days o Patients with a history of CNS metastases who have completed local therapy with surgical resection and/or radiation therapy are eligible o Patients may have CNS metastases that are stable or progressing radiologically. If patients have progressive brain metastases, they should be asymptomatic from their CNS disease. o Patients with current evidence of leptomeningeal disease are not eligible o Patients may have untreated brain metastases or previously treated brain metastases, as long as no immediate local CNS-directed therapy is indicated o Any prior whole brain radiation therapy must have been completed > 14 days prior to the date of Enrollment o Prior stereotactic brain radiosurgery is permitted at any time prior to Enrollment o CNS surgical resection must have been completed > 28 days prior to the date of Enrollment; patient must have complete recovery from surgery 6. Documented (including de novo): (a) locally advanced breast cancer that is not considered curable by surgery and/or radiation; or (b) metastatic breast cancer (MBC) 7. 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 8. Cohort 2 only: Prior endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor unless endocrine therapy is not indicated (ie, short relapse-free interval while on adjuvant endocrine therapy [endocrine resistance]; rapidly progressing disease/visceral crisis; or endocrine intolerance). Any prior targeted therapies are permitted. There is no limit to the number of prior endocrine therapies. 9. 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. In addition to any tissue used for PD-L1 testing to determine eligibility, a tumor block or 15 slides from a newly obtained or archival core or excisional biopsy of a not-previously-irradiated tumor lesion obtained since completion of any systemic therapy (metastatic tumor lesion preferred) must be submitted for central PD-L1 testing. If tumor block or 15 slides are unavailable or if biopsy is thought to be unsafe, discuss with Sponsor whether patient can be enrolled. 10. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 11. Adequate
Exclusion criteria
Exclusion criteria: 1. Prior chemotherapy for locally advanced or metastatic disease 2. 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 3. Current evidence or history of leptomeningeal disease 4. Other cancer that required therapy within the preceding 5 years other than adequately treated: (a) non-melanoma skin cancer or in situ cancer; or (b) following approval by the Sponsor medical team, other cancer that has a very low risk of interfering with the safety or efficacy endpoints of the Study 5. Known human immunodeficiency virus infection, unless well controlled. Patients who are on an adequate antiviral regimen with no evidence of active infection are considered well controlled. 6. Known active hepatitis B or known active hepatitis C infection 7. 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 and, in the judgment of the Investigator, would make the patient inappropriate for entry into this Study 8. Presence of neuropathy Grade > 1 per NCI CTCAE version 5.0 9. History of hypersensitivity to any of the Study drugs or any of their ingredients, as applicable 10. 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; the following are exceptions to this exclusion criterion: o Intranasal, inhaled, or topical steroids, or local steroid injections (eg, intraarticular injection) o Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent o Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent; patients with Type 1 diabetes, vitiligo, psoriasis, hypothyroid disease, celiac disease or hyperthyroid disease not requiring immunosuppressive treatment are eligible 11. Anticancer treatment, including endocrine therapy, radiotherapy (except stereotactic brain radiosurgery), chemotherapy or biologic therapy, = 14 days prior to Enrollment 12. Major surgery = 28 days prior to Enrollment; patient must have complete recovery from surgery 13. 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 (patients should discontinue taking any regularly-taken medication that is a strong inhibitor or inducer of the CYP3A pathway) 14. Pregnant or breastfeeding 15. If, in the opinion of the Investigator, the patient is deemed unwilling or unable to comply with the requirements of the Study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary: Cohort 1: To assess the antitumor activity of tesetaxel in combination with one of three different programmed cell death protein 1 or programmed death-ligand 1 (PD-(L)1) inhibitors (including a randomized comparison of the antitumor activity with nivolumab, pembrolizumab, or atezolizumab) in patients with previously untreated, triple-negative MBC as assessed by objective response rate (ORR) and progression free survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Cohort 2: To assess the antitumor activity of tesetaxel monotherapy in elderly patients with HER2 negative MBC previously untreated with chemotherapy in the MBC setting as assessed by ORR by RECIST 1.1;Primary end point(s): Primary Efficacy Endpoints: Objective response rate (ORR) as assessed by the Investigators using RECIST 1.1 criteria Cohort 1 only: Progression-free survival (PFS) as assessed by the Investigators using RECIST 1.1 criteria;Timepoint(s) of evaluation of this end point: The primary analysis for PFS in Cohort 1 is scheduled after at least 70% of patients have had a PFS event or have been permanently censored for the PFS outcome.;Secondary Objective: Secondary: Cohort 1: To assess the safety and tolerability of tesetaxel in combination with one of three different PD-(L)1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) in patients with previously untreated, triple-negative MBC Cohort 2: To assess the safety and tolerability of tesetaxel monotherapy in elderly patients with HER2 negative MBC previously untreated with chemotherapy in the MBC setting | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: Cohort 2 only: PFS as assessed by the Investigators using RECIST 1.1 criteria Duration of response (DoR) as assessed by the Investigators using RECIST 1.1 criteria Overall survival (OS) Exploratory Efficacy Endpoints: Cohort 1 only: ORR by PD-L1 expression as determined by central PD-L1 testing, where tumor response status is assessed by the Investigators using RECIST 1.1 criteria Cohort 1 only: PFS by PD-L1 expression as determined by central PD-L1 testing, where tumor response status is assessed by the Investigators using RECIST 1.1 criteria Cohort 2 only: ORR by receptor subtype (HR positive subgroup and triple-negative subgroup), where tumor response status is assessed by the Investigators using RECIST 1.1 criteria CNS ORR as assessed by the Investigators in patients with CNS metastases at baseline CNS DoR as assessed by the Investigators in patients with CNS metastases at baseline Safety Endpoints: Treatment-emergent adverse events (TEAEs), including deaths and other serious adverse events (SAEs) Immune-related adverse events (AEs) Clinical laboratory abnormalities ;Timepoint(s) of evaluation of this end point: Secondary Outcome: Cohort 1: DoR [Time Frame: Approx. 2.5-3.5 years], OS [4.0-5.0 yrs] Cohort 2: PFS [2.5-3.5 yrs], DoR [2.5-3.5 yrs], OS [4.0-5.0 yrs] Others: Cohort 1: ORR by PD-L1 expression [2 - 3 yrs]; PFS by PD-L1 expression [2.5-3.5 yrs];CNS ORR in pts with CNS metastases at baseline [2-3 yrs];CNS DoR in pts with CNS metastases at baseline [2.5-3.5 yrs] Cohort 2: ORR by receptor subtype for the HR positive and triple-negative subgroups [2-3yrs];CNS ORR in patients with CNS metastases at baseline [2-3 yrs]; CNS DoR in patients with CNS metastases at baseline [2.5-3.5 yrs] Safety analysis : A Data Safety Monitoring Committee will conduct periodic reviews of safety data, including an interim analysis of the first 6 pts who have completed the first cycle of therapy in Cohort 1. | — |
Countries
Australia, Belgium, Canada, France, Germany, Korea, Republic of, Poland, Russian Federation, Singapore, Spain, Taiwan, Ukraine, United States
Contacts
Public ContactChief Development Officer
Odonate Therapeutics, Inc.
Outcome results
None listed