Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma
Conditions
Brief summary
This phase II trial studies how well a cancer vaccine called STEMVAC works in combination with chemotherapy in treating patients with PD-L1 negative, triple-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). STEMVAC is designed to target proteins that are expressed on breast cancer stem cells, and it is believed to work by boosting the immune system to recognize and destroy the invader tumor cells that are causing the disease. Chemotherapy drugs 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. Giving STEMVAC in combination with chemotherapy may be an effective treatment for PD-L1 negative metastatic triple-negative breast cancer.
Detailed description
OUTLINE: Patients receive systemic standard of care chemotherapy as determined by their attending medical oncologist. Patients receive 3 priming doses of STEMVAC with sargramostim intradermally (ID) every 21-28 days (7-13 days after each chemotherapy administration or during the off week of weekly chemotherapy), 2 booster STEMVAC/sargramostim doses at 4 and 7 months after 3rd priming dose, and then every 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or ultrasound-guided biopsy, for research purposes, on study, as well as CT or positron emission tomography (PET) scans and blood sample collection throughout the study. In addition, patients may also undergo CT or ultrasound-guided biopsy, for research purposes, during screening. After completion of study treatment, patients are followed up at 21 or 28 days and then every 6 months for 3 years.
Interventions
Given ID
DRUGChemotherapy
Given standard of care chemotherapy
PROCEDUREComputed Tomography
Undergo CT scans
PROCEDUREComputed Tomography Assisted Biopsy
Undergo CT-guided biopsy
BIOLOGICALSargramostim
Given ID
PROCEDUREUltrasound-Guided Biopsy
Undergo ultrasound-guided biopsy
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREPositron Emission Tomography (PET)
Undergo PET scan
Sponsors
University of Washington
Kuni Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be at least ≥ 18 years of age * Note: Because no dosing or adverse event (AE) data are currently available on the use of STEMVAC in patients \< 18 years of age, children and adolescents are excluded from this study, but will be eligible for future pediatric trials, if applicable * Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status Score of ≤ 2 * Histologically confirmed triple-negative breast cancer * Tumors with estrogen receptor (ER)-low (≤ 5%) or negative and progesterone receptor (PR)-low (≤ 5%) or negative will be included * HER2-negative or HER2-low will be defined by the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2023 "Human Epidermal Growth Factor Receptor 2 (HER2) Breast Testing Guideline Update" which reaffirms the 2018 "HER2 Breast Testing Guideline Focused Update" * Tumor is negative for PD-L1 marker testing per standard of care immunohistochemistry 22C3 pharmDx assay * Metastatic disease that is measurable based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions * Have at least 1 site of disease confirmed by the treating oncologist that could be biopsied during treatment. This site should not be a site that is used to determine measurable disease for efficacy purposes. Lesions that will be biopsied should not be in a previously irradiated area unless progression has been demonstrated in such lesions * Patients should not have received any prior cancer immunotherapy in the metastatic setting * Prior Food and Drug Administration (FDA)-approved antibody drug conjugates are allowed * Patients are appropriate candidates to receive standard of care chemotherapy as per treating oncologist's clinical judgement * Patients who have received prior neoadjuvant or adjuvant chemotherapy are allowed * A minimum of 14 days washout since last systemic therapy or any palliative radiotherapy is required * Treatment with a bisphosphate or denosumab concurrently with protocol-specific therapy is allowed while on study (it is not exclusionary) * Patients must be at least 28 days post systemic steroids prior to enrollment, unless this is a steroid administered concurrently with chemotherapy or used as part of prophylaxis to prevent intravenous (IV) contrast reactions * Must have recovered from major infections and/or surgical procedures; and in the opinion of the investigator, not have any significant active concurrent medical illnesses or condition precluding protocol treatment * Willing to undergo up to two serial biopsies while on study * White blood cell (WBC) ≥ 2500/mm\^3 (Within 28 days of receiving first study vaccine) * Lymphocyte count ≥ 500/mm\^3 (Within 28 days of receiving first study vaccine) * Absolute neutrophil count (ANC) ≥ 1000/μL (Within 28 days of receiving first study vaccine) * Hemoglobin (Hgb) ≥ 9 g/dL (Within 28 days of receiving first study vaccine) * Platelets ≥ 75,000/μL (Within 28 days of receiving first study vaccine) * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be \< 3.0 mg/dL (Within 28 days of receiving first study vaccine) * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN (Within 28 days of receiving first study vaccine) * Creatinine ≤ 1.5 x ULN mg/dL or creatinine clearance \> 60 mL/min (Within 28 days of receiving first study vaccine) * Patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a person of child-bearing potential. Acceptable methods of contraception are abstinence, condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. Effective methods of contraception must be used throughout the study until the end of treatment on study
Exclusion criteria
* Patient has received more than one line of prior therapy in metastatic setting * Patients with tumors that are PD-L1-positive per standard of care immunohistochemistry 22C3 pharmDx assay * Enrollment in a concurrent interventional clinical trial. Biomarker or tissue collection or any other non-interventional clinical trial enrollment is allowed * Patients with any of the following cardiac conditions: * Symptomatic restrictive cardiomyopathy * Dilated cardiomyopathy * Unstable angina within 4 months prior to enrollment * New York Heart Association functional class III-IV heart failure on active treatment * Symptomatic pericardial effusion * Patients with any autoimmune disease or comorbidities that require chronic systemic steroids or immunosuppressants. Patients with conditions requiring inhaled, intranasal or topical steroids are permitted * Known hypersensitivity reaction to the granulocyte-macrophage colony stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF * A non-breast malignancy requiring radiation or systemic therapy within last 5 years or any B-cell malignancy (e.g., chronic lymphocytic leukemia or follicular lymphoma) under active surveillance * Pregnant and breastfeeding individuals * Known history of human immunodeficiency virus (HIV) infection, hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive), or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected) * Major surgery within the 4 weeks prior to initiation of study vaccine * Must be 14 days between a non-study vaccine, including live attenuated and non-live vaccines and any STEMVAC vaccination * Note: The minimum of 14 days does not apply to the tetanus and diphtheria (Td) vaccine * Any condition that may interfere with the patient's participation in the study per treating physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of immunogenicity of CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid vaccine (STEMVAC): Incidence of patients who develop a positive immunogenic response after vaccination | Baseline up to 7 months after STEMVAC priming dose #3 | The Th1 STEMVAC antigen specific immune response will be determined by IFN-gamma ELISPOT. Magnitude of Th1 response will be defined for each antigen in STEMVAC for each patient as the value of the corrected spots per well (CSPW) (CSPW= \[(mean of spots in the antigen stimulated wells) - (mean of antigens for the no-antigen negative control wells)\] for the same time point). Patients are considered to have preexisting immune response if the mean of spots in antigen wells is greater than the mean + 2 standard deviations of no-antigen wells at baseline. Patients are considered to have generated or enhanced antigen specific immunity post-vaccine if the maximal corrected IFN-gamma response post-vaccine is greater than the mean + 2 standard deviations of the baseline level (p \< 0.05). A patient will be considered an immunogenic responder if they develop an antigen-specific immune response to at least 1 of the 5 vaccine antigens. |
| Incidence of adverse events | Up to 21 or 28 days after completion of study treatment | Will be determined by chemical and clinical parameters evaluated at various time points. Toxicity grading will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 6.0 and monitoring of adverse events will be done per Food and Drug Administration and NCI guidelines. Descriptive statistics will be provided on the key demographic and clinical variables, such as mean, standard deviation, and range for continuous variables, and percent and number for categorical variables, such as toxicity grades. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6-month overall response rate | At 6 months | Will evaluate the clinical response to treatment following the first booster dose of STEMVAC using standard of care imaging and RECIST 1.1. |
| Progression-free survival (PFS) | From the start of treatment to the worsening of cancer or death whichever occurs first, assessed up to 3 years after completion of study treatment | Will evaluate the real-world progression-free survival to first subsequent therapy, defined as the date of first subsequent therapy after STEMVAC immunization and chemotherapy to disease progression, initiation of hospice or death as extracted from clinical notes. |
| Overall survival (OS) | Up to 3 years after completion of study treatment | Overall survival will be defined by patient survival or death from the start of treatment. |
| Magnitude of immunogenicity of CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid vaccine (STEMVAC) | Baseline up to 7 months after STEMVAC priming dose #3 | Defined as the sum of the interferon gamma enzyme-linked immunosorbent spot of all STEMVAC antigens on blood samples collected pre-vaccine as compared to 1-month post dose #3 of the STEMVAC vaccine and again after 2 booster doses of STEMVAC vaccine. The magnitude of immunity will be calculated as the sum of antigen-specific immune responses across the five vaccine antigens. The mean and maximum post-vaccine immune responses will be summarized and compared with pre-treatment levels. If substantial outliers are present or the data are non-normally distributed, the Wilcoxon signed-rank test will be used to assess differences between pre-treatment and post-vaccine priming samples. |
Countries
United States
Contacts
CONTACTResearch Coordinator(s)
PRINCIPAL_INVESTIGATORBrie Chun, MD
Fred Hutch/University of Washington Cancer Consortium
Outcome results
None listed