/A

Phase 1

• Conditions: Breast cancer; MedDRA version: 21.1Level: PTClassification code 10061020Term: Breast cancer maleSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10057654Term: Breast cancer femaleSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10006201Term: Breast cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10006202Term: Breast cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004715-41-FR
• Lead Sponsor: Odonate Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-11-29
• Last Update Posted: 10 August 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 130

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 central nervous system (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: For central determination of PD-L1 expression, adequate, 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); if tumor block or 15 slides are unavailable or if biopsy thought to be unsafe,
discuss with Sponsor whether patient can be enrolled (PD-L1 positive expression not required for Study entry)
10. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
11. Adequate bone marrow, hepatic, and renal function, as evidenced by:
Absolute neutrophil count (ANC) = 1,500/µL without colony-stimulating factor support
Platelet count = 100,000/µL
Hemoglobin = 9 g/dL withou

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified