Pilot Study of the Feasibility and Safety of a Personalized Peptide Vaccine in Patients With Advanced Pancreatic Ductal Adenocarcinoma or Colorectal Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Proportion of enrolled patients for whom a personalized vaccine is developed and ready to administer (cohorts A and B)
研究概览
简要总结
This phase I trial studies the side effects and best way to give personalized peptide vaccine in patients with pancreatic or colorectal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Personalized peptide vaccine is a vaccine developed from patient's own tumor cells and blood in order to use as a biological therapy. Biological therapies, such as personalized peptide vaccine may attack tumor cells and stop them from growing or kill them.
详细描述
PRIMARY OBJECTIVES:
I. Demonstrate that developing a custom vaccine for metastatic pancreatic ductal adenocarcinoma (PDA) and colorectal cancer (CRC) patients is feasible. (cohorts A and B)
II. Show that a custom peptide-based vaccine in combination with imiquiomod, pembrolizumab, and/or sotigalimab (APX005M) is safe. (cohorts A and B and C and D)
SECONDARY OBJECTIVES:
I. Determine the clinical benefit of the peptide vaccine alone or combined with pembrolizumab or pembrolizumab and APX005M. (cohorts A and B and C and D)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Metastatic CRC or PDA planned to or have undergone complete surgical resection (metastatectomy) and also for PDA participants with localized disease planned for primary tumor resection.
- •Any lines (including zero) of therapy prior to tissue harvest.
- •Adequate tumor tissue availability
- •Adults (age ≥ 18)
- •ECOG PS 0-1
- •Life expectancy >12 months for Cohort C and >9 months for Cohort D
- •Adequate organ and marrow function
- •Ability to understand and the willingness to sign a written informed consent document.
- •As the effects of a peptide based vaccine, pembrolizumab or APX005M on the developing human fetus are unknown, women of child-bearing potential and men must agree to use adequate contraception at study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant, she should inform her treating physician immediately. Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), sexually active participants must use birth control during and for >120 days after the study. Abstinence is also an acceptable form of birth control.
- •For Cohort C only: participants must have metastatic CRC and are planned to or have undergone complete metastecomy/ies and agree to have post-operative blood draw for ctDNA testing within 6 weeks following surgical resection.
排除标准
- •History of HIV or AIDS
- •Patients with brain metastasis
- •Serious autoimmune conditions
- •Use of chronic immune suppressive medications.
- •Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Women of child bearing potential who are pregnant or breastfeeding. Women with a positive pregnancy test at enrollment or prior to administration of vaccine. .
- •Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
- •Known history of active TB (Bacillus Tuberculosis).
- •Hypersensitivity to therapy drugs or their components.
- •Has a known additional malignancy that is progressing or requires active treatment.
- •Active coagulopathy.
- •History of arterial thrombosis within 3 months prior to starting study treatment.
- •History of New York Heart Association Class 3-4 heart failure or myocardial infarction within 6 months prior to starting therapy.
- •Known history of Hepatitis B or known active Hepatitis C.
研究组 & 干预措施
Cohort A (personalized vaccine, imiquimod)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients then receive imiquimod cream topically in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
干预措施: Synthetic Tumor-Associated Peptide Vaccine Therapy (Biological)
Cohort A (personalized vaccine, imiquimod)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients then receive imiquimod cream topically in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
干预措施: Imiquimod (Drug)
Cohort B (personalized vaccine, imiquimod, pembrolizumab)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
干预措施: Imiquimod (Drug)
Cohort A (personalized vaccine, imiquimod)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients then receive imiquimod cream topically in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
干预措施: Computed Tomography (Procedure)
Cohort A (personalized vaccine, imiquimod)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients then receive imiquimod cream topically in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
干预措施: Magnetic Resonance Imaging (Procedure)
Cohort B (personalized vaccine, imiquimod, pembrolizumab)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
干预措施: Synthetic Tumor-Associated Peptide Vaccine Therapy (Biological)
Cohort B (personalized vaccine, imiquimod, pembrolizumab)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
干预措施: Magnetic Resonance Imaging (Procedure)
Cohort C and D (vaccine, imiquimod, pembrolizumab, APX005M)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Beginning about 1 hour after each vaccine, patients also receive sotigalimab IV over 60 minutes on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and weeks 6,12, and 24, then every 3 months, and at week 39.
干预措施: Synthetic Tumor-Associated Peptide Vaccine Therapy (Biological)
Cohort C and D (vaccine, imiquimod, pembrolizumab, APX005M)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Beginning about 1 hour after each vaccine, patients also receive sotigalimab IV over 60 minutes on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and weeks 6,12, and 24, then every 3 months, and at week 39.
干预措施: Computed Tomography (Procedure)
Cohort C and D (vaccine, imiquimod, pembrolizumab, APX005M)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Beginning about 1 hour after each vaccine, patients also receive sotigalimab IV over 60 minutes on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and weeks 6,12, and 24, then every 3 months, and at week 39.
干预措施: Magnetic Resonance Imaging (Procedure)
Cohort B (personalized vaccine, imiquimod, pembrolizumab)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
干预措施: Computed Tomography (Procedure)
Cohort C and D (vaccine, imiquimod, pembrolizumab, APX005M)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Beginning about 1 hour after each vaccine, patients also receive sotigalimab IV over 60 minutes on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and weeks 6,12, and 24, then every 3 months, and at week 39.
干预措施: Imiquimod (Drug)
Cohort B (personalized vaccine, imiquimod, pembrolizumab)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
干预措施: Pembrolizumab (Biological)
Cohort C and D (vaccine, imiquimod, pembrolizumab, APX005M)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Beginning about 1 hour after each vaccine, patients also receive sotigalimab IV over 60 minutes on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and weeks 6,12, and 24, then every 3 months, and at week 39.
干预措施: Sotigalimab (Biological)
Cohort C and D (vaccine, imiquimod, pembrolizumab, APX005M)
Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Beginning about 1 hour after each vaccine, patients also receive sotigalimab IV over 60 minutes on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and weeks 6,12, and 24, then every 3 months, and at week 39.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Proportion of enrolled patients for whom a personalized vaccine is developed and ready to administer (cohorts A and B)
时间窗: Up to 12 weeks post-enrollment
Proportion of enrolled patients who receive at least 1 dose of vaccine at any time post-enrollment (cohorts A and B)
时间窗: Up to 44 weeks
Incidence of adverse events (AEs)
时间窗: Up to 24 weeks
Defined as the proportion of subjects who experience at least one toxicity event per National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0. A toxicity event is defined as at least one grade 3 or 4 non-hematologic or grade 4 hematologic toxicity. Proportion of patients with AEs will be estimated, along with the Bayesian 95% credible interval.
次要结局
- Proportion of patients who have received at least one dose of vaccine that is alive and progression free defined based on response criteria according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(At 12 weeks post-vaccination (second re-staging scan))
- Progression-free survival (cohorts A and B and C)(The time between the date of first vaccination and evidence of progression on computed tomography scan or the date of death due to any cause, assessed up to 6 months after the last dose of vaccine)
- Response rate (cohort A and B)(Up to 12 weeks)
- Change in tumor biomarker (CA19-9, carcinoembryonic antigen [CEA] or circulating free deoxyribonucleic acid [cfDNA] mutation)(Up to 6 months)
- Overall survival(The time from first vaccination to death, assessed up to 6 months after the last dose of vaccine)
- Recurrence-free survival (cohort C and D)(Up to 6 months)
- Rate of circulating deoxyribonucleic acid (ctDNA) clearance (cohort C and D)(Up to 6 months)
- Change in neoantigen-specific T cell response (cohort C and D)(Baseline to 12 weeks after initiation of personalized peptide vaccination)
- Correlation of T-cell activation against vaccinated peptides and ctDNA dynamics (cohort C and D)(Up to 6 months)
- Tumor microenvironment immune infiltration and progression biopsies (cohort C and D)(Baseline, up to 6 months)
- T cell IFN-gamma release in response to selected personalized peptide antigens(Up to 6 months)
- Levels of intracellular cytokine staining of T cells(Up to 6 months)