RECRUITING

Neoantigen-based Personalized DNA Vaccine With Retifanlimab PD-1 Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma

Conditions

Unmethylated Glioblastoma glioblastoma neoantigen vaccine PD-1 blockade unmethylated MGMT

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a single institution, open-label, multi-arm, phase I study assessing the safety and immunogenicity of a personalized neoantigen-based personalized DNA vaccine combined with PD-1 blockade therapy in subjects with newly diagnosed, MGMT promoter unmethylated glioblastoma (GBM). Immune checkpoint blockade, specifically those targeting the PD-1/PD-L1 pathways, has shown efficacy in multiple solid and hematologic malignancies. Furthermore, as has been demonstrated in metastatic melanoma, combining PD-1/PD-L1 blockade with other immune checkpoint inhibitors has shown improved objective response rates, though there is a significant increase in serious immune-related adverse events. As such, current trials are exploring different doses, administration schedules, and immune checkpoint agents. One alternative approach, however, is to introduce a tumor-directed therapy such as a personalized neoantigen vaccine combined with these immune modulating agents (i.e. immune checkpoint blocking antibodies) to maximize the tumor-specific response but minimize the toxicity associated with increasing non-specific systemic immune activation by generating a potent and focused neoantigen specific immune response. This study will test the hypothesis that a personalized neoantigen DNA vaccine in combination with concurrent administration of immune checkpoint blockade therapy will enhance the magnitude and breadth of neoantigen-specific T cell responses while maintaining an acceptable safety profile. The overall goal of this study is to identify the optimal vaccine plus adjuvant platform that can be tested in a subsequent phase II study to determine the efficacy of a personalized neoantigen vaccine approach in patients with GBM.

Official Title

A Pilot Study to Assess the Safety and Immunogenicity of a Neoantigen-based Personalized DNA Vaccine With Retifanlimab PD-1 Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma

Quick Facts

Study Start:2023-10-27

Study Completion:2027-10-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05743595

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
Age 18 years or older Willing and able to provide informed consent Able to understand and follow study procedures Stable medical condition	* As this study aims to assess the immunogenicity of a personalized neoantigen DNA vaccine in combination with checkpoint blockade, 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. * 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 any agents used in the study. * History of immunodeficiency disorder or autoimmune condition requiring active 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 acute or chronic bleeding or clotting disorder that would contraindicate IM injections. * Presence of a cardioverter-defibrillator or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the intended deltoid injection site (unless deemed acceptable by a Cardiologist). * Presence of any metal implants or implantable medical device within the electroporation area. * Any active uncontrolled neurologic disorder, including seizures and epilepsy. * Recurrent known vasovagal-related syncopal episodes resulting in loss of consciousness. * Individuals in whom skin pinch thickness for all eligible injection sites exceeds 50 mm. * Individuals in whom the ability to observe possible local reactions at the eligible injection sites is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art. * History of organ transplant, including allogeneic stem cell transplantation. * Receiving any other investigational agents within 4 weeks of beginning study treatment. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic antibiotics or antifungal treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Evidence of interstitial lung disease, history of interstitial lung disease, or active, non-infectious pneumonitis. * 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. * Has received a live vaccine within 28 days of the planned start of study drug. Participants may receive the COVID-19 vaccine as long as it is not a live vaccine. COVID-19 vaccination will be captured in the eCRF as a concomitant medication. Administration of study treatment may be delayed to ensure vaccination is completed. * Active HBV or HCV infection that requires treatment. Hepatitis B virus DNA and HCV RNA must be undetectable upon testing. Participants who have cleared a prior HBV infection (defined as HBsAg negative, hepatitis B surface antibody positive, hepatitis B core antibody positive) are eligible for the study. * Note: For participants with cleared prior HBV infection, HBV prophylaxis should be considered per the investigator's discretion. Monitor for HBV reactivation every 3 cycles by performing HBV viral load and HBsAg serology test. Additional viral serologic testing may be performed at the investigator's discretion. * Note: Participants with no prior history of HBV infection who have been vaccinated against HBV and who have a positive test result for antibody to hepatitis B surface antigen as the only evidence of prior exposure may participate in the study. * Note: Hepatitis C antibody-positive participants who received and completed treatment for hepatitis C that was intended to eradicate the virus may participate if HCV RNA levels are undetectable.

Inclusion Criteria

Exclusion Criteria

Age 18 years or older
Willing and able to provide informed consent
Able to understand and follow study procedures
Stable medical condition

* As this study aims to assess the immunogenicity of a personalized neoantigen DNA vaccine in combination with checkpoint blockade, 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.
* 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 any agents used in the study.
* History of immunodeficiency disorder or autoimmune condition requiring active 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 acute or chronic bleeding or clotting disorder that would contraindicate IM injections.
* Presence of a cardioverter-defibrillator or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the intended deltoid injection site (unless deemed acceptable by a Cardiologist).
* Presence of any metal implants or implantable medical device within the electroporation area.
* Any active uncontrolled neurologic disorder, including seizures and epilepsy.
* Recurrent known vasovagal-related syncopal episodes resulting in loss of consciousness.
* Individuals in whom skin pinch thickness for all eligible injection sites exceeds 50 mm.
* Individuals in whom the ability to observe possible local reactions at the eligible injection sites is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art.
* History of organ transplant, including allogeneic stem cell transplantation.
* Receiving any other investigational agents within 4 weeks of beginning study treatment.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic antibiotics or antifungal treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Evidence of interstitial lung disease, history of interstitial lung disease, or active, non-infectious pneumonitis.
* 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.
* Has received a live vaccine within 28 days of the planned start of study drug. Participants may receive the COVID-19 vaccine as long as it is not a live vaccine. COVID-19 vaccination will be captured in the eCRF as a concomitant medication. Administration of study treatment may be delayed to ensure vaccination is completed.
* Active HBV or HCV infection that requires treatment. Hepatitis B virus DNA and HCV RNA must be undetectable upon testing. Participants who have cleared a prior HBV infection (defined as HBsAg negative, hepatitis B surface antibody positive, hepatitis B core antibody positive) are eligible for the study.
* Note: For participants with cleared prior HBV infection, HBV prophylaxis should be considered per the investigator's discretion. Monitor for HBV reactivation every 3 cycles by performing HBV viral load and HBsAg serology test. Additional viral serologic testing may be performed at the investigator's discretion.
* Note: Participants with no prior history of HBV infection who have been vaccinated against HBV and who have a positive test result for antibody to hepatitis B surface antigen as the only evidence of prior exposure may participate in the study.
* Note: Hepatitis C antibody-positive participants who received and completed treatment for hepatitis C that was intended to eradicate the virus may participate if HCV RNA levels are undetectable.

Contacts and Locations

Study Contact

Tanner M Johanns, M.D., Ph.D.

CONTACT

314-273-2723

tannerjohanns@wustl.edu

Principal Investigator

Tanner M Johanns, M.D., Ph.D.

PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Study Locations (Sites)

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Collaborators and Investigators

Sponsor: Washington University School of Medicine

Tanner M Johanns, M.D., Ph.D., PRINCIPAL_INVESTIGATOR, Washington University School of Medicine

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-10-27

Study Completion Date2027-10-31

Study Record Updates

Study Start Date2023-10-27

Study Completion Date2027-10-31

Terms related to this study

Keywords Provided by Researchers

glioblastoma
neoantigen vaccine
PD-1 blockade
unmethylated MGMT

Additional Relevant MeSH Terms

Unmethylated Glioblastoma