Recruiting

Phase 2

Durvalumab, Tremelimumab, ChemotherapyTesting the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer

Sponsor:

National Cancer Institute (NCI)

Code:

NCT03606967

Conditions

Anatomic Stage IV Breast Cancer AJCC v8

Invasive Breast Carcinoma

Metastatic Triple-Negative Breast Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Carboplatin

Computed Tomography

Durvalumab

Study Details

Brief summary:

This phase II trial studies how well nab-paclitaxel, durvalumab, and tremelimumab with or without personalized synthetic long peptide vaccine (neoantigen vaccine) works in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known whether giving nab-paclitaxel, durvalumab, and tremelimumab with or without neoantigen vaccine will work better in treating patients with triple negative breast cancer.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8

Invasive Breast Carcinoma

Metastatic Triple-Negative Breast Carcinoma

Study ID

NCT03606967

Start date

Apr 13, 2021

Status verified date

Jul, 2026

Completion date

Dec 30, 2026

Anticipated

Primary completion date

Dec 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Patients must have a histologically confirmed diagnosis of metastatic invasive triple negative breast cancer. Patients with clinical and/or radiologic suspicion of metastatic TNBC can be consented prior to this confirmation.
Estrogen receptor (ER) and progesterone receptor (PR) less than Allred score of 3 OR less than 1% positive staining cells in the invasive component of the tumor.
HER2 negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+.
PD-L1 negative by a Clinical Laboratory Improvement Act (CLIA) approved laboratory using compatible assays appropriate for treatment decisions.
Patients may have measurable or evaluable disease.
Patients must be willing to undergo biopsy and have accessible lesions for a new biopsy, or they must have sufficient tissue available from a biopsy performed for standard of care (specifications below). If patient does not have enough archived tissue available, a new biopsy is required. A tumor specimen obtained from relapsed primary, metastatic, or locally advanced sites of disease (if applicable) must be submitted. Acceptable samples include core needle biopsies for deep tumor tissue (minimum 4 cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. Formalin-fixed, paraffin-embedded (FFPE) tumor specimens in paraffin blocks are preferred; FFPE tumor tissue sections on slides may be provided if sufficient material (15 x 10μ, unstained) is available. Fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable.
No prior therapy for metastatic TNBC. Patients who have received taxane-based adjuvant therapy are required to have a disease-free interval of at least 12 months after completion of taxane therapy.
Age >= 18 years. Because no dosing or adverse event data are currently available on the use of durvalumab (MEDI4736) and tremelimumab in combination with neoantigen vaccine in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 60%).
Body weight > 30 kg.
Must have a life expectancy of at least 12 weeks.
Absolute neutrophil count >= 1,500/mcL.
Platelets >= 100,000/mcL.
Hemoglobin >= 9.0 g/dL.
Serum bilirubin =< 1.5 x institutional upper limit of normal.
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =< 5 x institutional upper limit of normal.
Calculated creatinine clearance > 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
The effects of durvalumab (MEDI4736) and tremelimumab and neoantigen vaccine on the developing human fetus are unknown. For this reason and because these agents may be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 180 days after completion of durvalumab (MEDI4736) and tremelimumab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Human immunodeficiency virus (HIV)-positive patients are eligible provided they have a negative viral load, CD4 count > 250, and are on a stable antiretroviral regimen.
Ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity who have a close caregiver or legal guardian are also eligible with the consent of the caregiver/guardian.

Exclusion Criteria:

Patients who are not considered to be candidates for carboplatin + gemcitabine for first line therapy of their metastatic triple negative breast cancer are not eligible.
Patients who have had chemotherapy, radiotherapy (to more than 30% of the bone marrow), or biologic therapy within 30 days (42 days for nitrosoureas or mitomycin C) prior to entering the study.
Patients who have received prior immunotherapy for metastatic disease.
Patients who have not recovered from grade >= 2 adverse events due to prior anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.

Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician.
Patients with grade >= 2 endocrinological adverse events (AEs), (e.g., hypothyroidism, adrenal insufficiency, hypopituitarism, or diabetes mellitus), must have been on a stable dose of supplemental therapy for at least 2 weeks before screening to be eligible for this study, and the endocrinological AE must be stable in the opinion of the treating physician.
Patients who are receiving any other investigational agents or who have received an investigational agent within the last 30 days.
Receipt of live attenuated vaccination within 6 months prior to study entry or within 30 days of receiving durvalumab (MEDI4736) and tremelimumab.

Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment.
Major surgical procedure within 28 days prior to the first dose of durvalumab (MEDI4736) and tremelimumab. Local surgery of isolated lesions for palliative intent is acceptable.
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab (MEDI4736) or tremelimumab. The following are exceptions to this criterion:

Intranasal, inhaled, topical steroids or local steroid injections (e.g. intra-articular injection)
Systemic corticosteroids at physiological doses which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid
Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
Steroids for symptoms from brain metastases as defined.
Spinal cord compression or active brain metastases and/or carcinomatous meningitis. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to registration are eligible if they meet all of the following criteria:

Residual neurological symptoms have resolved to grade =< 2
On stable doses of dexamethasone, if applicable and if acceptable in the opinion of the treating physician
Follow-up MRI performed after surgery or completion of radiation therapy and prior to registration shows no new lesions.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab (MEDI4736) and tremelimumab. Known allergy, or history of serious adverse reaction to vaccines, such as anaphylaxis, hives or respiratory difficulty.
Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 470 ms calculated from 3 electrocardiograms (ECGs) (within 15 minutes at 5 \[+/- 3\] minutes apart).
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, evidence of any acute or chronic viral illness or disease, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because durvalumab (MEDI4736) and tremelimumab has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with durvalumab (MEDI4736) and tremelimumab, breastfeeding should be discontinued if the mother is treated with durvalumab (MEDI4736) and tremelimumab. These potential risks may also apply to other agents used in this study. A negative serum pregnancy test is required no more than 7 days before study entry.
Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
History of pneumonitis or interstitial lung disease.
History of active primary immunodeficiency.
Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and tuberculosis \[TB\] testing in line with local practice), hepatitis B (known positive hepatitis B virus \[HBV\] surface antigen \[HBsAg\] result), or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
The patient with a previous history of non-breast malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided the following criteria are met:

Patient has undergone potentially curative therapy for all prior malignancies.
Patients have been considered disease free for at least 1 year (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).
Patients with a strong likelihood of non-adherence (such as difficulties in adhering to follow-up schedule due to geographic distance from the treatment facility) should not be knowingly registered.
History of allogeneic organ transplantation.

Study Design

Enrollment

86 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (neoantigen vaccine, durvalumab, nab-paclitaxel)

See Detailed Description.

active comparator: Arm II (durvalumab, nab-paclitaxel)

See Detailed Description.

Interventions

Biopsy Procedure

Undergo tumor biopsy

Biospecimen Collection

Undergo blood and urine sample collection

Carboplatin

Given IV

Computed Tomography

Undergo CT scan

Durvalumab

Given IV

Gemcitabine Hydrochloride

Given IV

Magnetic Resonance Imaging

Undergo MRI

Nab-paclitaxel

Given IV

Personalized Synthetic Long Peptide Vaccine

Given SC

Poly ICLC

Given SC

Sacituzumab Govitecan

Given IV

Tremelimumab

Given IV

Primary outcome measure

Progression-free survival (PFS) [ Time Frame: From initiation of Part B to progression or death, assessed at 6 and 12 months ]

Central Contacts and Locations

Locations

UCHealth University of Colorado Hospital

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Site Public Contact

Principal Investigator:

Jennifer R. Diamond

UM Sylvester Comprehensive Cancer Center at Aventura

Recruiting

Aventura, Florida, United States, 33180

Contacts

Site Public Contact

Principal Investigator:

Alejandra T. Perez

UM Sylvester Comprehensive Cancer Center at Coral Gables

Recruiting

Coral Gables, Florida, United States, 33146

Contacts

Site Public Contact

Principal Investigator:

Alejandra T. Perez

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Recruiting

Deerfield Beach, Florida, United States, 33442

Contacts

Site Public Contact

Principal Investigator:

Alejandra T. Perez

University of Miami Miller School of Medicine-Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Contacts

Site Public Contact

Principal Investigator:

Alejandra T. Perez

UM Sylvester Comprehensive Cancer Center at Kendall

Recruiting

Miami, Florida, United States, 33176

Contacts

Site Public Contact

Principal Investigator:

Alejandra T. Perez

UM Sylvester Comprehensive Cancer Center at Plantation

Recruiting

Plantation, Florida, United States, 33324

Contacts

Site Public Contact

Principal Investigator:

Alejandra T. Perez

Moffitt Cancer Center-International Plaza

Recruiting

Tampa, Florida, United States, 33607

Contacts

Site Public Contact

800-679-0775 ClinicalTrials@moffitt.org

Principal Investigator:

Aixa E. Soyano

Moffitt Cancer Center - McKinley Campus

Recruiting

Tampa, Florida, United States, 33612

Contacts

Site Public Contact

800-679-0775 ClinicalTrials@moffitt.org

Principal Investigator:

Aixa E. Soyano

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Contacts

Site Public Contact

800-679-0775 ClinicalTrials@moffitt.org

Principal Investigator:

Aixa E. Soyano

Moffitt Cancer Center at Wesley Chapel

Recruiting

Wesley Chapel, Florida, United States, 33544

Contacts

Site Public Contact

800-679-0775 ClinicalTrials@moffitt.org

Principal Investigator:

Aixa E. Soyano

Johns Hopkins University/Sidney Kimmel Cancer Center

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Site Public Contact

410-955-8804 jhcccro@jhmi.edu

Principal Investigator:

Cesar A. Santa-Maria

Siteman Cancer Center at Saint Peters Hospital

Recruiting

City of Saint Peters, Missouri, United States, 63376

Contacts

Site Public Contact

800-600-3606 info@siteman.wustl.edu

Principal Investigator:

William E. Gillanders

Siteman Cancer Center at West County Hospital

Recruiting

Creve Coeur, Missouri, United States, 63141

Contacts

Site Public Contact

800-600-3606 info@siteman.wustl.edu

Principal Investigator:

William E. Gillanders

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Site Public Contact

800-600-3606 info@siteman.wustl.edu

Principal Investigator:

William E. Gillanders

Siteman Cancer Center-South County

Recruiting

St Louis, Missouri, United States, 63129

Contacts

Site Public Contact

800-600-3606 info@siteman.wustl.edu

Principal Investigator:

William E. Gillanders

Siteman Cancer Center at Christian Hospital

Recruiting

St Louis, Missouri, United States, 63136

Contacts

Site Public Contact

800-600-3606 info@siteman.wustl.edu

Principal Investigator:

William E. Gillanders

NYP/Weill Cornell Medical Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

Principal Investigator:

Massimo Cristofanilli

Wake Forest University at Clemmons

Recruiting

Clemmons, North Carolina, United States, 27012

Contacts

Site Public Contact

Principal Investigator:

Emily H. Douglas

Wake Forest University Health Sciences

Recruiting

Winston-Salem, North Carolina, United States, 27157

Contacts

Site Public Contact

Principal Investigator:

Emily H. Douglas

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066 Jamesline@osumc.edu

Principal Investigator:

Kai C. Johnson

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

Principal Investigator:

Julia Foldi

VCU Massey Comprehensive Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Site Public Contact

804-628-6430 CTOclinops@vcu.edu

Principal Investigator:

Masey M. Ross

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 10, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-10.