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Neoantigen-based Personalized Vaccine Combined With Immune Checkpoint Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma
A Pilot Study to Assess the Safety, Feasibility, and Immunogenicity of a Neoantigen-based Personalized Vaccine Combined With Immune Checkpoint Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma
1 other identifier
interventional
3
1 country
1
Brief Summary
This is a single institution, open-label, multi-arm, pilot study assessing the safety, feasibility, and immunogenicity of a personalized neoantigen-based vaccine plus poly-ICLC (NeoVax) combined with immune checkpoint inhibitors in subjects with newly diagnosed, unmethylated glioblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2018
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 29, 2018
CompletedFirst Posted
Study publicly available on registry
February 5, 2018
CompletedStudy Start
First participant enrolled
October 31, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 26, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2020
CompletedOctober 27, 2021
October 1, 2021
1.5 years
January 29, 2018
October 26, 2021
Conditions
Outcome Measures
Primary Outcomes (4)
Safety and tolerability of regimen as measured by a <= 33% dose-limiting toxicity (DLT) rate for a given cohort
* The DLT observation period is 60 days after C1D1 for patients enrolled to Cohorts A, C, and D and is 90 days after C1D1 for patients enrolled to Cohorts B and E. * DLT is defined as any grade 3 or greater event that occurs during the DLT observation period that is considered at least possibly related to the study treatment.
Up to 90 days after start of treatment
Feasibility of generating a personalized neoantigen peptide vaccine as measured by the ability to identify candidate tumor-specific neoantigens
From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)
Feasibility of generating a personalized neoantigen peptide vaccine as measured by the the ability to manufacture a neoantigen-based synthetic long peptide vaccine
From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)
Feasibility of generating a personalized neoantigen peptide vaccine as measured by the ability to administer the vaccine to a patient at 4 weeks post-completion of radiotherapy
From time of resection to 4 weeks post-radiation therapy (approximately 14 weeks)
Secondary Outcomes (7)
Immunogenicity of a personalized neoantigen peptide vaccine as measured by the ability to generate a measurable neoantigen-specific T cell response in vaccinated patients
Week 4 post-vaccination
Immunogenicity of a personalized neoantigen peptide vaccine as measured by the ability to generate a measurable neoantigen-specific T cell response in vaccinated patients
Week 16 post-vaccination
Immunogenicity of a personalized neoantigen peptide vaccine as measured by the number of individual neoantigens per number of neoantigens vaccinated against, with which a measurable T cell-specific response
Week 4 post-vaccination
Immunogenicity of a personalized neoantigen peptide vaccine as measured by the number of individual neoantigens per number of neoantigens vaccinated against, with which a measurable T cell-specific response
Week 16 post-vaccination
Number of high quality candidate neoantigens present in patients with newly diagnosed glioblastoma
Up to 2 weeks post sequencing
- +2 more secondary outcomes
Study Arms (5)
Cohort A: NeoVax+Nivolumab (start at time of progression)
EXPERIMENTAL* NeoVax given on Days 1, 8, 15, and 22 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase) * Nivolumab 480 mg i.v. given on Day 1 of each cycle beginning at time of progression
Cohort B: NeoVax+Nivolumab (start with Cycle 2)
EXPERIMENTAL* NeoVax given on Days 1, 8, 15, and 22 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase) * Nivolumab 480 mg i.v. given on Day 1 of each cycle beginning with Cycle 2 (start of boosting phase)
Cohort C: NeoVax + Nivolumab (start with Cycle 1)
EXPERIMENTAL* NeoVax given on Days 1, 8, 15, and 22 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase) * Nivolumab 480 mg i.v. given on Day 1 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase)
Cohort D: NeoVax+Ipilimumab+Nivolumab (start with Cycle 3)
EXPERIMENTAL* NeoVax given on Days 1, 8, 15, and 22 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase) * Ipilimumab 1 mg/kg i.v. given on Days 1 and 22 of Cycle 1 (priming phase) * Nivolumab 480 mg i.v. given on Day 1 of Cycle 3 and then on Day 1 of each subsequent cycle
Cohort E: NeoVax+Ipilimumab+Nivolumab (day 1&15 each cycle)
EXPERIMENTAL* NeoVax given on Days 1, 8, 15, and 22 of Cycle 1 (priming phase), and then on Day 1 of each subsequent cycle (boosting phase) * Ipilimumab 1 mg/kg i.v. given every 6 weeks beginning on Day 1 of Cycle 1 (C1D1, C2D15, C4D1, C5D15, C7D1, C8D15 …) * Nivolumab 3 mg/kg i.v. given on Days 1 and 15 of each cycle (q2w) beginning on Day 1 of Cycle 1
Interventions
At each vaccination time point, patients will receive up to 20 synthetic long peptides co-administered with 1.5 mg of poly-ICLC divided into a maximum of four injections (pools). Each pool (of vaccine + poly IC:LC) will be administered to one of the four limbs (right axilla, left axilla, right inguina, left inguina) by subcutaneous injection.
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Ipilimumab is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)
-Baseline, cycle 2 day 1, cycle 4 day 1, and time of progression or discontinuation of treatment
-Baseline, cycle 4 day 1, and time of progression or discontinuation of treatment
Eligibility Criteria
You may qualify if:
- Newly diagnosed histologically confirmed unmethylated glioblastoma multiforme (WHO grade IV). Patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded. Unmethylated MGMT must be confirmed by a PCR-based assay.
- Patients who had craniotomy with biopsy, subtotal resection, total gross resection, or re-resection will be permitted.
- Consented to genome sequencing and dbGaP-based data sharing and has provided or will provide germline (PBMC) and tumor DNA/RNA samples of adequate quality for sequencing. (Acquisition of specimens for sequencing and the sequencing itself may be done as part of routine care or another research project.)
- At least 18 years of age.
- Karnofsky performance status ≥ 60%
- Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Systemic corticosteroid therapy is permitted provided dosing is no greater than 4 mg per day (dexamethasone or equivalent) on the day of vaccine administration.
- Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation, including at least 5 months (for women of childbearing potential) and at least 7 months (for men) after last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
You may not qualify if:
- As this study aims to assess the immunogenicity of various vaccine plus adjuvant combinations, no prior immunotherapy will be permitted.
- Inadequate tissue acquisition to allow for neoantigen screening.
- No candidate neoantigen identified during screening.
- A history of other malignancy ≤ 3 years previous with the exception of non-melanoma skin cancer, any in situ cancer that has been successfully resected and cured, treated superficial bladder cancer, or any early-stage solid tumor that was successfully resected without need for adjuvant radiation or chemotherapy.
- Receiving any other investigational agents within 4 weeks of beginning study treatment.
- Known allergy, or history of serious adverse reaction to, vaccines such as anaphylaxis, hives, or respiratory difficulty.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to poly-ICLC or other agents used in the study.
- Uncontrolled intercurrent 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.
- History of pre-existing immunodeficiency disorder or autoimmune condition requiring immunosuppressive therapy. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines.
- Presence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatment.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of first dose of vaccine.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Washington University School of Medicinelead
- Bristol-Myers Squibbcollaborator
Study Sites (1)
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Tanner Johanns, M.D., Ph.D.
Washington University School of Medicine
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
January 29, 2018
First Posted
February 5, 2018
Study Start
October 31, 2018
Primary Completion
April 26, 2020
Study Completion
December 31, 2020
Last Updated
October 27, 2021
Record last verified: 2021-10
Data Sharing
- IPD Sharing
- Will not share