Ignite Creation Date:
2025-12-24 @ 4:16 PM
Ignite Modification Date:
2025-12-26 @ 5:49 AM
Study NCT ID:
NCT05078866
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-10-17
First Post:
2021-10-14
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase Ib/II Clinical Trial of Nous-209 for Recurrent Neoantigen Immunogenicity and Cancer Immune Interception in Lynch Syndrome
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib/II trial evaluates the safety and effect of the Nous-209 vaccine in Lynch syndrome patients. Lynch syndrome is an inherited disorder in which affected individuals have a higher-than-normal chance of developing colorectal cancer and certain other types of cancer, often before the age of 50. In Lynch syndrome, errors in the genetic information inside cells are not properly corrected. When that happens, the cells produce new proteins called neoantigens. Neoantigens are recognized by the body's immune system as foreign, and the body tries to get rid of them. Nous-209 is a vaccine made with man-made copies of some of those neoantigens. This trial aims to see whether the Nous-209 vaccine is safe to give to patients with Lynch syndrome, whether people are able to take the Nous-209 vaccine without becoming too uncomfortable, and how the immune system of patients with Lynch syndrome respond to the Nous-209 vaccine. This trial may help researchers determine whether receiving Nous-209 have an effect on the development of polyps or tumors in the colon.
Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of adenoviral tumor-specific neoantigen priming vaccine GAd-209-FSP (GAd20-209-FSPs) (1 prime) and MVA tumor-specific neoantigen boosting vaccine MVA-209-FSP (MVA-209-FSPs) (1 boost) vaccination when administered as a single agent (monotherapy) in participants with Lynch syndrome (LS).
II. To evaluate the neoantigen-specific immunogenicity of GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 boost) vaccination when administered as a single agent (monotherapy) in participants with LS.
III. To evaluate the neoantigen-specific immunogenicity of GAd20-209-FSP prime and MVA-209-FSP boost or MVA-209-FSP boost alone when administered to previously-vaccinated immunogenic participants with LS.
IV. To evaluate the safety and tolerability of GAd20-209-FSP prime and MVA-209-FSP boost or MVA-209-FSP boost alone when administered to previously vaccinated immunogenic participants with LS.
SECONDARY OBJECTIVES:
I. To assess the effect of Nous-209 vaccination on T cell immune profile and T cell receptor (TCR) repertoire in the peripheral blood of participants with LS.
II. To assess the effect of Nous-209 vaccination on TCR repertoire within histologically normal colorectal mucosal of participants with LS.
III. To evaluate the effect of Nous-209 vaccination on tumor infiltrating lymphocyte (TIL) immune profile and TCR repertoire within colorectal adenomas in participants with LS.
IV. To assess the cytotoxicity of matched T cells on participant-derived colorectal adenoma organoids following Nous-209 vaccination in participants with LS.
V. To evaluate the effect of Nous-209 vaccination on the burden of colorectal adenomas/advanced neoplasia/carcinoma in participants with LS.
VI. To assess the effect of Nous-209 vaccination on the burden of LS-related carcinomas in participants with LS.
VII. To evaluate the effect of Nous-209 vaccination on cell free deoxyribonucleic acid (DNA) (cfDNA) mutation profiles and cfDNA burden in participants with LS.
VIII. To correlate tobacco and alcohol consumption with the immune response to Nous-209 in trial participants.
IX. To assess the mismatch repair (MMR) and/or microsatellite instability (MSI) status of polyps (and adjacent normal mucosa as control) detected in the baseline and end-of-the-study colonoscopy using different technologies such as immunohistochemistry, MSI analysis by polymerase chain reaction (PCR), or next-generation sequencing.
OUTLINE:
PART I: Patients receive GAd20-209-FSPs intramuscularly (IM) on day 1 and MVA-209-FSPs IM at week 8. Patients undergo endoscopy with biopsy during screening and follow up as well as blood sample collection on the trial.
PART II: Eligible patients from Part I are randomized to 1 of 2 arms.
ARM A: Patients receive GAd20-209-FSPs IM at week 52 and MVA-209-FSPs IM at week 60. Patients undergo endoscopy with biopsy as well as blood sample collection on the trial.
ARM B: Patients receive MVA-209-FSPs IM at week 52. Patients undergo endoscopy with biopsy as well as blood sample collection on the trial.
After completion of study treatment, patients are followed up at weeks 16, 24, 36, and 52.
I. To evaluate the safety and tolerability of adenoviral tumor-specific neoantigen priming vaccine GAd-209-FSP (GAd20-209-FSPs) (1 prime) and MVA tumor-specific neoantigen boosting vaccine MVA-209-FSP (MVA-209-FSPs) (1 boost) vaccination when administered as a single agent (monotherapy) in participants with Lynch syndrome (LS).
II. To evaluate the neoantigen-specific immunogenicity of GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 boost) vaccination when administered as a single agent (monotherapy) in participants with LS.
III. To evaluate the neoantigen-specific immunogenicity of GAd20-209-FSP prime and MVA-209-FSP boost or MVA-209-FSP boost alone when administered to previously-vaccinated immunogenic participants with LS.
IV. To evaluate the safety and tolerability of GAd20-209-FSP prime and MVA-209-FSP boost or MVA-209-FSP boost alone when administered to previously vaccinated immunogenic participants with LS.
SECONDARY OBJECTIVES:
I. To assess the effect of Nous-209 vaccination on T cell immune profile and T cell receptor (TCR) repertoire in the peripheral blood of participants with LS.
II. To assess the effect of Nous-209 vaccination on TCR repertoire within histologically normal colorectal mucosal of participants with LS.
III. To evaluate the effect of Nous-209 vaccination on tumor infiltrating lymphocyte (TIL) immune profile and TCR repertoire within colorectal adenomas in participants with LS.
IV. To assess the cytotoxicity of matched T cells on participant-derived colorectal adenoma organoids following Nous-209 vaccination in participants with LS.
V. To evaluate the effect of Nous-209 vaccination on the burden of colorectal adenomas/advanced neoplasia/carcinoma in participants with LS.
VI. To assess the effect of Nous-209 vaccination on the burden of LS-related carcinomas in participants with LS.
VII. To evaluate the effect of Nous-209 vaccination on cell free deoxyribonucleic acid (DNA) (cfDNA) mutation profiles and cfDNA burden in participants with LS.
VIII. To correlate tobacco and alcohol consumption with the immune response to Nous-209 in trial participants.
IX. To assess the mismatch repair (MMR) and/or microsatellite instability (MSI) status of polyps (and adjacent normal mucosa as control) detected in the baseline and end-of-the-study colonoscopy using different technologies such as immunohistochemistry, MSI analysis by polymerase chain reaction (PCR), or next-generation sequencing.
OUTLINE:
PART I: Patients receive GAd20-209-FSPs intramuscularly (IM) on day 1 and MVA-209-FSPs IM at week 8. Patients undergo endoscopy with biopsy during screening and follow up as well as blood sample collection on the trial.
PART II: Eligible patients from Part I are randomized to 1 of 2 arms.
ARM A: Patients receive GAd20-209-FSPs IM at week 52 and MVA-209-FSPs IM at week 60. Patients undergo endoscopy with biopsy as well as blood sample collection on the trial.
ARM B: Patients receive MVA-209-FSPs IM at week 52. Patients undergo endoscopy with biopsy as well as blood sample collection on the trial.
After completion of study treatment, patients are followed up at weeks 16, 24, 36, and 52.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2021-10799 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 2022-0065 | OTHER | M D Anderson Cancer Center | View | |
| MDA21-06-01 | OTHER | DCP | View | |
| P30CA016672 | NIH | None | https://reporter.nih.gov/quic… | View |
| UG1CA242609 | NIH | None | https://reporter.nih.gov/quic… | View |