A Phase I/II Study of Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab in Advanced Solid Tumors (PNeoVCA)
概览
- 阶段
- 1 期
- 干预措施
- Biopsy
- 疾病 / 适应症
- Anatomic Stage III Breast Cancer AJCC v8
- 发起方
- Mayo Clinic
- 入组人数
- 132
- 试验地点
- 1
- 主要终点
- Incidence of adverse events (Phase I)
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
This phase I/II trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.
详细描述
PRIMARY OBJECTIVE: I. To evaluate the safety of personalized neoantigen peptide vaccine in combination with pembrolizumab in advanced solid cancers. (Phase I) II. To evaluate and estimate 24-months event-free survival (EFS) rate per Kaplan-Meier method in triple-negative breast cancer (TNBC) patients with residual cancer burden-2 and 3 (RCB-2 and RCB-3) after neoadjuvant pembrolizumab-based chemotherapy treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 3) III. To evaluate and estimate 24-months event-free survival (DFS) rate per Kaplan-Meier method in stage II/III non-small cell lung cancer (NSCLC) patients after surgery treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 4) SECONDARY OBJECTIVES: I. To evaluate and estimate the immunogenicity response rate in patients with advanced solid cancers receiving personalized neoantigen peptide vaccine in combination with pembrolizumab. (Phase I) II. To obtain preliminary information on the immunogenicity of neoantigen in induction of specific cellular immune responses and humoral immune response. III. To evaluate and estimate the immunogenicity response rate in TNBC patients with residual cancer burden-2 and 3 (RCB-2 and RCB-3) after neoadjuvant pembrolizumab-based chemotherapy treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 3) IV. To evaluate adverse event profile in in TNBC patients with residual cancer burden-2 and 3 (RCB-2 and RCB-3) after neoadjuvant pembrolizumab-based chemotherapy treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 3) V. To evaluate and estimate the vaccine immunogenicity response rate in stage II/III NSCLC patients after surgery treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 4) VI. To evaluate adverse event profile in stage II/III NSCLC patients after surgery treated with neoantigen vaccine in combination with pembrolizumab. (Phase II Cohort 4) EXPLORATORY OBJECTIVES: I. To obtain preliminary information on the immunogenicity of neoantigen in induction of specific cellular immune responses and humoral immune response in patients with selected advanced solid tumors. (Phase I) II. To obtain preliminary estimates of efficacy as measured by objective response rate (ORR based on Response Evaluation Criteria in Solid Tumors \[RECIST\]) of personalized neoantigen peptide vaccine and pembrolizumab in patients with selected advanced solid tumors. (Phase I) III. To obtain preliminary information of immunity persistence, as well as pre-existing immunity in patients with selected advanced solid tumors. (Phase I) IV. To obtain preliminary information on the immunogenicity of neoantigen in induction of specific cellular immune responses and humoral immune response in Cohort 1 (TNBC patients with RCB-2 and RCB-3) and 2 (stage II/III NSCLC patients) separately. (Phase II) V. To obtain preliminary information of immunity persistence, as well as pre-existing immunity in Cohort 1 (TNBC patients with RCB-2 and RCB-3) and 2 (stage II/III NSCLC patients) separately. (Phase II) OUTLINE: This is a phase I, dose-escalation study of personalized neoantigen vaccine followed by a phase II study. Patients are assigned to 1 of 4 cohorts. COHORT 1- \*NO LONGER ENROLLING\*: Patients receive cyclophosphamide intravenously (IV) on day -3. Patients then receive personalized neoantigen vaccine with sargramostim (GM-CSF) subcutaneously (SC) on days 1, 4, 8, and 15 of cycle 1 and on day 1 of cycle 2 in the absence of disease progression or unacceptable toxicity. COHORT 2 - \*NO LONGER ENROLLING\*: Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. COHORT 3: Patients with TNBC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. COHORT 4: Patients with NSCLC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up at 30 days and then every 3 months up to 2 years from study enrollment.
研究者
入排标准
入选标准
- •COHORT 1 and COHORT 2 are no longer enrolling.
- •PHASE I PRE-REGISTRATION, ALL:
- •Willing to provide tissue specimens per protocol
- •NOTE: includes fresh tissue specimen at pre-registration for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo Institutional Review Board (IRB) protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and/or registration.
- •Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease
- •NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
- •Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy
- •Provide written informed consent
- •Willing to return to enrolling institution for follow-up
- •Willing to provide blood specimens for research
排除标准
- •ALL PHASES:
- •Any of the following because study involves investigational agent whose genotoxic, mutagenic and teratogenic effects on developing fetus and newborn are unknown:
- •Pregnant person
- •Nursing person unwilling to stop breast feeding
- •Person of childbearing potential unwilling to employ adequate contraception from registration through 6 months after final vaccine cycle
- •Co-morbid systemic illnesses or other severe concurrent disease which, in judgment of investigator, would make patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and toxicity of prescribed regimens
- •History of myocardial infarction =\< 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
- •Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
- •PHASE I PRE-REGISTRATION:
- •Acute, reversible effect(s) of prior therapy not recovered to baseline regardless of interval since last treatment
研究组 & 干预措施
Cohort 1(cyclophosphamide, vaccine) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and on day 1 of cycle 2 in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Biopsy
Cohort 1(cyclophosphamide, vaccine) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and on day 1 of cycle 2 in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Cyclophosphamide
Cohort 1(cyclophosphamide, vaccine) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and on day 1 of cycle 2 in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Neoantigen Peptide Vaccine
Cohort 1(cyclophosphamide, vaccine) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and on day 1 of cycle 2 in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Sargramostim
Cohort 1(cyclophosphamide, vaccine) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and on day 1 of cycle 2 in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Biospecimen Collection
Cohort 1(cyclophosphamide, vaccine) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and on day 1 of cycle 2 in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Computed Tomography
Cohort 1(cyclophosphamide, vaccine) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and on day 1 of cycle 2 in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Magnetic Resonance Imaging
Cohort 2 (cyclophophamide, vaccine, pembrolizumab) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Cyclophosphamide
Cohort 2 (cyclophophamide, vaccine, pembrolizumab) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Neoantigen Peptide Vaccine
Cohort 2 (cyclophophamide, vaccine, pembrolizumab) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Pembrolizumab
Cohort 2 (cyclophophamide, vaccine, pembrolizumab) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Sargramostim
Cohort 2 (cyclophophamide, vaccine, pembrolizumab) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Biospecimen Collection
Cohort 2 (cyclophophamide, vaccine, pembrolizumab) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Biopsy
Cohort 2 (cyclophophamide, vaccine, pembrolizumab) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Computed Tomography
Cohort 2 (cyclophophamide, vaccine, pembrolizumab) ** NO LONGER ENROLLING **
NO LONGER ENROLLING Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Magnetic Resonance Imaging
Cohort 3 (cyclophosphamide, vaccine, pembrolizumab)
Patients with TNBC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Cyclophosphamide
Cohort 3 (cyclophosphamide, vaccine, pembrolizumab)
Patients with TNBC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Neoantigen Peptide Vaccine
Cohort 3 (cyclophosphamide, vaccine, pembrolizumab)
Patients with TNBC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Pembrolizumab
Cohort 3 (cyclophosphamide, vaccine, pembrolizumab)
Patients with TNBC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Sargramostim
Cohort 3 (cyclophosphamide, vaccine, pembrolizumab)
Patients with TNBC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Biospecimen Collection
Cohort 3 (cyclophosphamide, vaccine, pembrolizumab)
Patients with TNBC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Biopsy
Cohort 3 (cyclophosphamide, vaccine, pembrolizumab)
Patients with TNBC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Computed Tomography
Cohort 3 (cyclophosphamide, vaccine, pembrolizumab)
Patients with TNBC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Magnetic Resonance Imaging
Cohort 4 (cyclophosphamide, vaccine, pembrolizumab)
Patients with NSCLC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Cyclophosphamide
Cohort 4 (cyclophosphamide, vaccine, pembrolizumab)
Patients with NSCLC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Neoantigen Peptide Vaccine
Cohort 4 (cyclophosphamide, vaccine, pembrolizumab)
Patients with NSCLC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Pembrolizumab
Cohort 4 (cyclophosphamide, vaccine, pembrolizumab)
Patients with NSCLC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Sargramostim
Cohort 4 (cyclophosphamide, vaccine, pembrolizumab)
Patients with NSCLC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Biospecimen Collection
Cohort 4 (cyclophosphamide, vaccine, pembrolizumab)
Patients with NSCLC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Biopsy
Cohort 4 (cyclophosphamide, vaccine, pembrolizumab)
Patients with NSCLC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Computed Tomography
Cohort 4 (cyclophosphamide, vaccine, pembrolizumab)
Patients with NSCLC receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with GM-CSF SC on days 1, 4, 8, and 15 of cycle 1 and then on day 1 of cycles 2, 5, and 8. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle or as clinically indicated. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy throughout the study. Additionally, patients undergo blood sample collection as well as CT or MRI throughout the study.
干预措施: Magnetic Resonance Imaging
结局指标
主要结局
Incidence of adverse events (Phase I)
时间窗: Up to 2 years from first vaccine administration
The number and severity (grade) of all treatment related adverse events (AEs) will be tabulated and summarized. Non-hematologic AEs will be evaluated via the ordinal CTCAE v5.0 standard AE grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTCAE v5.0 standard AE grading. Both all grade and grade 3 and above AEs will be described and summarized in a similar fashion. Overall AE incidences as well as AE profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
Maximally tolerated dose (MTD) (Phase I)
时间窗: Up to 2 years
MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. For instance, those toxicities with an incidence of at least 25% will be observed with a probability of at least 82% (1-(1-0.25).
Dose LImiting Toxicity (DLT) (Phase I)
时间窗: Up to 2 years
DLT are defined to be adverse event (AE) occurring from day -3 through day 35 that is possibly, probably, or definitely related to neoantigen peptide vaccine with/without pembrolizumab and fulfills any of the following criteria using the National Cancer Institute's Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), version (v) 5.0
Event free survival (EFS) (Phase II Cohort 3)
时间窗: Up to 2 years
EFS is defined as the length of time after primary treatment for a cancer ends until occurrence of complications or events that the treatment was intended to prevent or delay.
Disease-free survival (DFS) (Phase II Cohort 4)
时间窗: Up to 2 years
DFS is defined as the length of time after primary treatment for a cancer ends until any signs or symptoms of that cancer recur.
次要结局
- The number and percentage of participants who completed the sequencing with satisfactory data quality registration and identified at least 10 actionable peptides, meet the eligibility criteria for registration, and able to initiate vaccine production(Up to 16 weeks)
- Immunogenicity responders(Within 24 weeks)
- Immunogenicity response rate (Phase I)(Within 24 weeks)
- Incidence of adverse events (Phase II)(Up to 2 years)
- Immunogenicity response rate (Phase II)(Within 24 weeks)