A Phase II Randomized Study of Safety and Efficacy of a Multiple Antigen Vaccine (STEMVAC) in Non-Small-Cell Lung Cancer Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- Change from baseline percentage of CD8+ TIL in patients between the two arms
研究概览
简要总结
This phase II trial tests whether CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine (STEMVAC) works to shrink tumors in patients with stage IV non-small cell lung cancer. STEMVAC targets specific immunogenic proteins that help lung cancer cells to grow. STEMVAC is made up of deoxyribonucleic acid (DNA), which is a natural substance in every living organism. DNA acts like a blueprint that tells all the cells in your body how to function. The DNA used in this study contains instructions for your body to produce parts of the 5 proteins the investigators identified (CDH3, CD105, YB-1, MDM2 and SOX2). STEMVAC is given with granulocyte-macrophage colony stimulating factor (GM-CSF) which is being used as an adjuvant to help create a stronger immune response. Giving STEMVAC with GM-CSF to patients while on maintenance therapy for non-small cell lung cancer (NSCLC) may help activate certain immune cells to recognize and kill lung cancer cells.
详细描述
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive STEMVAC intradermally (ID) and sargramostim ID on day 14 of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo computed tomography (CT) and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
ARM II: Patients receive sargramostim ID on day 14 of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
After completion of study treatment, patients are followed up twice yearly for up to 5 years.
This study previously closed to accrual in 2025. The study reopened at the University of Nebraska in 2026.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
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
- •Histologically-confirmed diagnosis of stage IV non-squamous or squamous NSCLC.
- •Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within one month of first vaccine. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- •Have completed 3-4 cycles of chemoimmunotherapy, without evidence of progressive disease. Pembrolizumab has to be included in at least 3 of these cycles.
- •Have not received more than 2 cycles of maintenance pembrolizumab and/or pemetrexed and be a candidate for continuation of this therapy.
- •At least 1 site of disease 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 on a previously irradiated area unless progression has been demonstrated in such lesions.
- •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.
- •Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 or
- •Patients must have recovered from major infections and/or surgical procedures, and in the opinion of a principle investigator (PI)/co-PI/study physician/physician extender, not have any significant active concurrent medical illnesses precluding protocol treatment.
- •Willing to undergo up to two serial biopsies while on study.
- •Estimated life expectancy of more than 6 months.
- •White blood cells (WBC) >= 3000/mm^3 (within 60 days of first vaccination).
- •Lymphocyte count >= 800/mm^3 (within 60 days of first vaccination).
- •Platelet count >= 75,000/mm^3 (within 60 days of first vaccination).
- •Hemoglobin (Hgb) >= 9 g/dl (within 60 days of first vaccination).
- •Serum creatinine =< 1.2 mg/dl or creatinine clearance > 50 ml/min (within 60 days of first vaccination).
- •Total bilirubin =< 1.5 mg/dl (within 60 days of first vaccination).
- •Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) =< 2 times upper limit of normal (ULN) or SGOT =< 5 times upper limit of normal (ULN) in the presence of liver metastasis (within 60 days of first vaccination).
- •If female of childbearing potential has a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
- •All patients who are having sex that can lead to pregnancy must agree to contraception for the duration of study.
- •Patients must be at least 18 years of age.
排除标准
- •Patients with any of the following cardiac conditions:
- •Symptomatic restrictive 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 central nervous system (CNS) metastasis that have not been treated. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases and also are off steroids for 2 weeks prior to dosing with study medication.
- •Patients with any contraindication to receiving recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF) based products.
- •Patients with any clinically significant autoimmune disease that requires active treatment with immunosuppressants. Replacement therapy (e.g., thyroxine, insulin) is not considered a form of systemic treatment. Administration of systemic steroids (i.e., for allergic reactions, computed tomography (CT) scans, or the management of immune related adverse events [irAEs]) is allowed.
- •Has a known history of another prior invasive malignancy within 2 years, except subjects with early stage cancer that has undergone potentially curative therapy with no evidence of that disease recurrence for 2 years since initiation of that therapy.
- •Patients who are simultaneously enrolled in any other treatment study.
- •Patients who are pregnant or breastfeeding.
- •Patients with genetic driver alterations (e.g EGFR, ALK, ROS1, BRAF, MET ex 14, RET) for which targeted treatment exist and are Food and Drug Association (FDA) approved, except if the subject is not eligible or has progressed through those therapies.
研究组 & 干预措施
Arm I (STEMVAC, sargramostim)
Patients receive STEMVAC ID and sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
干预措施: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine (Biological)
Arm I (STEMVAC, sargramostim)
Patients receive STEMVAC ID and sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
干预措施: Biopsy (Procedure)
Arm II (sargramostim)
Patients receive sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
干预措施: Computed Tomography (Procedure)
Arm II (sargramostim)
Patients receive sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
干预措施: Biopsy (Procedure)
Arm II (sargramostim)
Patients receive sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
干预措施: Biospecimen Collection (Procedure)
Arm I (STEMVAC, sargramostim)
Patients receive STEMVAC ID and sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
干预措施: Computed Tomography (Procedure)
Arm I (STEMVAC, sargramostim)
Patients receive STEMVAC ID and sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
干预措施: Biospecimen Collection (Procedure)
Arm I (STEMVAC, sargramostim)
Patients receive STEMVAC ID and sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
干预措施: Sargramostim (Biological)
Arm II (sargramostim)
Patients receive sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.
干预措施: Sargramostim (Biological)
结局指标
主要结局
Change from baseline percentage of CD8+ TIL in patients between the two arms
时间窗: Baseline and after the third vaccine (at approximately 12 weeks)
Immunohistochemical (IHC) staining for CD3, CD4, and CD8 will be performed on the biopsies collected pre-treatment and post 3 vaccine administration. Two-sample Student's t-test with a 1-sided 0.05 significance level will be used to assess the difference. The distribution of the differences of CD8 T-cells between baseline and post treatment will be examined to check the normality assumption and outliers. If the outliers are substantial or the distribution is skewed, Wilcoxon nonparametric test will be used to assess the difference between the two treatment arms. Depending on the correlation between baseline and post-treatment measures, alternative analytical method will be adopted using an ordinary least square regression for the post-treatment CD8 T-cells percentage while adjusting for the baseline measure.
Incidence of adverse events
时间窗: Up to 1 year
Will be evaluated using the modified National Cancer Institute (NCI) toxicity criteria. Toxicity evaluation will be based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0
CD8 is Reported as a Fraction of CD3+ Tumor Infiltrating Lymphocytes (TIL) in 4 High-power Field (HPF)
时间窗: Baseline and after the third vaccine (at approximately 12 weeks)
Immunohistochemical (IHC) staining for CD8+ CD3+ will be performed on the biopsies collected pre-treatment and post 3rd vaccine administration.
Number of Participants With Recorded Adverse Event(s)
时间窗: Up to 20 weeks
Will be evaluated using the modified National Cancer Institute (NCI) toxicity criteria. Toxicity evaluation will be based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0
次要结局
- Progression free survival (PFS)(Up to 5 years)
- Overall survival (OS)(Up to 5 years)
- Magnitude of the immune response to CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine (STEMVAC)(Up to 1 year)
- Vaccine induced T-cells traffic to tumor(Up to 1 year)
- Overall response rate (ORR)(1 month after the 3rd vaccine (Up to 6 months))
- T-cell activation and Type I lymphocyte markers(Up to 1 year)
- Magnitude of the Immune Response to CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine (STEMVAC)(Up to 1 year)
- Vaccine Induced T-cells Traffic to Tumor(Up to 1 year)
- Overall Response Rate (ORR)(1 month after the 3rd vaccine (Up to 6 months))
- Progression Free Survival (PFS)(Up to 5 years)
- Overall Survival (OS)(Up to 5 years)
- T-cell Activation and Type I Lymphocyte Markers(Up to 1 year)
研究者
Mary (Nora) Disis
Professor
University of Washington