A Phase II Trial of the Immunogenicity of a DNA Plasmid-Based Vaccine (STEMVAC) Encoding Th1 Selective Epitopes From Five Antigens Associated With Breast Cancer Stem Cells (MDM2, YB1, SOX2, CDH3, CD105) in Patients With Metastatic Triple-Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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 image-guided biopsy, for research purposes, on study, as well as computed tomography (CT) or positron emission tomography (PET) scans and blood sample collection throughout the study. In addition, patients may also undergo image-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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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. Lesions that will be biopsied should not be in a previously irradiated area unless progression has been demonstrated in such lesions
- •Patients can 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) ≥ 2.5 THOU/uL (Within 28 days of receiving first study vaccine)
- •Lymphocyte count ≥ 0.5 THOU/uL (Within 28 days of receiving first study vaccine)
- •Absolute neutrophil count (ANC) ≥ 1.0 THOU/uL (Within 28 days of receiving first study vaccine)
- •Hemoglobin (Hgb) ≥ 9 g/dL (Within 28 days of receiving first study vaccine)
- •Platelets ≥ 75 THOU/uL (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/d (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
排除标准
- •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. Participation in a trial for chimeric antigen receptor (CAR)-T cell therapy may be permitted if the CAR-T cell therapy is not planned to occur until after the currently proposed treatment (i.e. no longer participating in STEMVAC and chemotherapy trial)
- •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
研究组 & 干预措施
Treatment (chemotherapy, STEMVAC, GM-CSF)
Patients receive systemic standard of care chemotherapy as determined by their attending medical oncologist. Patients receive 3 priming doses of STEMVAC with sargramostim 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 image-guided biopsy, for research purposes, on study, as well as CT or PET scans and blood sample collection throughout the study. In addition, patients may also undergo image-guided biopsy, for research purposes, during screening.
干预措施: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine (Biological)
Treatment (chemotherapy, STEMVAC, GM-CSF)
Patients receive systemic standard of care chemotherapy as determined by their attending medical oncologist. Patients receive 3 priming doses of STEMVAC with sargramostim 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 image-guided biopsy, for research purposes, on study, as well as CT or PET scans and blood sample collection throughout the study. In addition, patients may also undergo image-guided biopsy, for research purposes, during screening.
干预措施: Computed Tomography (Procedure)
Treatment (chemotherapy, STEMVAC, GM-CSF)
Patients receive systemic standard of care chemotherapy as determined by their attending medical oncologist. Patients receive 3 priming doses of STEMVAC with sargramostim 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 image-guided biopsy, for research purposes, on study, as well as CT or PET scans and blood sample collection throughout the study. In addition, patients may also undergo image-guided biopsy, for research purposes, during screening.
干预措施: Sargramostim (Biological)
Treatment (chemotherapy, STEMVAC, GM-CSF)
Patients receive systemic standard of care chemotherapy as determined by their attending medical oncologist. Patients receive 3 priming doses of STEMVAC with sargramostim 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 image-guided biopsy, for research purposes, on study, as well as CT or PET scans and blood sample collection throughout the study. In addition, patients may also undergo image-guided biopsy, for research purposes, during screening.
干预措施: Biospecimen Collection (Procedure)
Treatment (chemotherapy, STEMVAC, GM-CSF)
Patients receive systemic standard of care chemotherapy as determined by their attending medical oncologist. Patients receive 3 priming doses of STEMVAC with sargramostim 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 image-guided biopsy, for research purposes, on study, as well as CT or PET scans and blood sample collection throughout the study. In addition, patients may also undergo image-guided biopsy, for research purposes, during screening.
干预措施: Positron Emission Tomography (PET) (Procedure)
结局指标
主要结局
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
时间窗: 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
时间窗: 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.
Progression-free survival (PFS)
时间窗: 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
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1/Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST). Kaplan-Meier method will be used to estimate PFS and the rates at specified time point (e.g., 6 or 12 months) will be calculated and the 95% confidence intervals will be provided.
次要结局
- Overall survival (OS)(Up to 3 years after completion of study treatment)
- 6-month overall response rate(At 6 months)
- 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)
- 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)
- Overall survival (OS)(Up to 3 years after completion of study treatment)
- Incidence of adverse events(Up to 21 or 28 days after completion of study treatment)
- Immunogenicity of CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid vaccine (STEMVAC)(Baseline up to 7 months after STEMVAC priming dose #3)