Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors
PNeoVCA
A Phase I/II Study of Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab in Advanced Solid Tumors (PNeoVCA)
3 other identifiers
interventional
132
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2022
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 25, 2022
CompletedFirst Posted
Study publicly available on registry
March 8, 2022
CompletedStudy Start
First participant enrolled
March 31, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2028
March 12, 2026
March 1, 2026
6 years
February 25, 2022
March 10, 2026
Conditions
Outcome Measures
Primary Outcomes (5)
Incidence of adverse events (Phase I)
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.
Up to 2 years from first vaccine administration
Maximally tolerated dose (MTD) (Phase I)
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).
Up to 2 years
Dose LImiting Toxicity (DLT) (Phase I)
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
Up to 2 years
Event free survival (EFS) (Phase II Cohort 3)
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.
Up to 2 years
Disease-free survival (DFS) (Phase II Cohort 4)
DFS is defined as the length of time after primary treatment for a cancer ends until any signs or symptoms of that cancer recur.
Up to 2 years
Secondary Outcomes (5)
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
Incidence of adverse events (Phase II)
Up to 2 years
Immunogenicity response rate (Phase I)
Within 24 weeks
Immunogenicity response rate (Phase II)
Within 24 weeks
Other Outcomes (3)
Objective response rate (Phase I)
Within 12 weeks
Persistence Immunogenicity response rate (Phase I and Phase II)
Within 24 weeks from baseline
Pre-existing Immunity (Phase I and Phase II)
Within 24 weeks from baseline
Study Arms (4)
Cohort 1(cyclophosphamide, vaccine) ** NO LONGER ENROLLING **
EXPERIMENTALNO 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.
Cohort 2 (cyclophophamide, vaccine, pembrolizumab) ** NO LONGER ENROLLING **
EXPERIMENTALNO 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.
Cohort 3 (cyclophosphamide, vaccine, pembrolizumab)
EXPERIMENTALPatients 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.
Cohort 4 (cyclophosphamide, vaccine, pembrolizumab)
EXPERIMENTALPatients 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.
Interventions
Given IV
Receive personalized neoantigen vaccine SC
Given IV
Given SC
Undergo blood sample collection
Undergo tissue biopsy
Undergo CT
Undergo MRI
Eligibility Criteria
You may qualify if:
- 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
- Negative pregnancy test =\< 7 days prior to pre-registration for persons of childbearing potential. If urine test cannot be confirmed negative, serum pregnancy test will be required.
- Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle
- Willing to receive tetanus vaccination if subject has not had one =\< 1 year prior to pre-registration
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
- Anticipated life expectancy \> 6 months
- The following lab values obtained =\< 28 days prior to pre-registration:
- +76 more criteria
You may not qualify if:
- 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
- Uncontrolled illness including, but not limited to:
- Ongoing or active infection
- Psychiatric illness/social situations
- Congestive heart failure with New York Heart Association (NYHA) class III or IV moderate to severe objective evidence of cardiovascular disease
- Stroke =\< 3 months prior to pre-registration
- +60 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (1)
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yanyan Lou, MD, PhD
Mayo Clinic
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 25, 2022
First Posted
March 8, 2022
Study Start
March 31, 2022
Primary Completion (Estimated)
March 31, 2028
Study Completion (Estimated)
March 31, 2028
Last Updated
March 12, 2026
Record last verified: 2026-03