Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients

Related Clinical Trial
Prostate Cancer Genetic Risk Evaluation and Screening Study Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients Overcoming Barriers to the Uptake of Cascade Screening for Lynch Syndrome: Workbook Feasibility Study Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome Evaluation of ArTificial Intelligence System (Gi-Genius) for adenoMa dEtection in Lynch Syndrome. DNA Adductomics for Colorectal Cancer Investigation PD-1 Antibody Following Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer Faecal Microbiota Characterization in Lynch Syndrome (LS) Patients With or Without Colorectal Neoplasia Evaluating the Cologuard Test for Use in Lynch Syndrome PD-1 Antibody for The Prevention of Adenomatous Polyps and Second Primary Tumors in Lynch Syndrome Patients Lynch Syndrome Can be Diagnosed Just From Somatic Mismatch Repair Mutation Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome Identifying and Caring for Individuals With Inherited Cancer Syndrome Predictive Factor Study of the Occurrence of Endometrial Cancer in Patients With Lynch Syndrome Liquid Biopsy Evaluation and Repository Development at Princess Margaret Direct Information to At-risk Relatives Family History Study on Cancer Risk Oxaliplatin, Leucovorin Calcium, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer Biomarkers in Samples From Patients With Endometrial Cancer Genetic Risk: Whether, When, and How to Tell Adolescents Familial Colorectal Cancer Registry in Hispanics Prostate Cancer Screening Among Men With High Risk Genetic Predisposition Collecting Information From Patients and Family Members With Hereditary Colorectal Cancer Syndromes or Who Are at High Risk of Developing Colorectal Cancer Identifying Patients With Hereditary and Familial Colorectal Cancer by Using an Online Risk Tool Pediatric Reporting of Adult-Onset Genomic Results Trial to Compare eConsent With Standard Consent Among Prospective Biobank Participants MSI in Circulatory DNA of Endometrial Cancer Telemedicine vs. Face-to-Face Cancer Genetic Counseling Educational CD-ROM Compared With Standard Informed Consent for Patients With Colorectal Cancer or a Family History of Colorectal Cancer Implementation of a New Strategy to Identify HNPCC Patients Energy Balance Interventions in Increasing Physical Activity in Breast Cancer Gene Positive Patients, Lynch Syndrome-Positive Patients, CLL Survivors or High-Risk Family Members Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes The GEOLynch Cohort Study Universal Endometrial Cancer DNA Sequencing for Detection of Lynch Syndrome and Personalized Care Weight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families Naproxen in Preventing DNA Mismatch Repair Deficient Colorectal Cancer in Patients With Lynch Syndrome Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland Omega 3 Fatty Acids in Colorectal Cancer (CRC) Prevention in Patients With Lynch Syndrome (COLYNE) NBI Versus Indigo Carmine During Colonoscopy in Lynch Syndrome I-Scan For Colon Polyp Detection In HNPCC Metagenomic Evaluation of the Gut Microbiome in Patients With Lynch Syndrome and Other Hereditary Colonic Polyposis Syndromes Psychosocial Aspects of Genetic Testing for Hereditary Nonpolyposis Colon Cancer Ohio Colorectal Cancer Prevention Initiative Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy Molecular Screening for Lynch Syndrome in Denmark Atorvastatin ± Aspirin in Lynch Syndrome Syndrome Diagnosis of Lynch Syndrome Based on Next-generation Sequencing in Colorectal Cancer Uncertain Genetic Test Results for Lynch Syndrome High Definition White-Light Colonoscopy vs. Chromoendoscopy for Surveillance of Lynch Syndrome. Linked Color Imaging Versus High-definition White Light Endoscopy for the Detection of Polyps in Patients With Lynch Syndrome (LCI-LYNCH) Hereditary Nonpolyposis Colorectal Cancer in Taiwan-Related Genetic Study and Clinical Applications Molecular Screening for Lynch Syndrome in Southern Denmark Universal Screening for Lynch Syndrome in Women With Endometrial and Non-Serous Ovarian Cancer Multi-Organ Screening Recommendations in Patients With Lynch Syndrome Diagnosis of Lynch Syndrome Based on Next-generation Sequencing in Patients Meeting Chinese Lynch Syndrome Criteria Chromoendoscopy to Decrease the Risk of Colorectal Neoplasia in Lynch Syndrome Effect of Chemoprevention by Low-dose Aspirin of New or Recurrent Colorectal Adenomas in Patients With Lynch Syndrome Integrating Genetic Testing for Lynch Syndrome in a Managed Care Setting Registry for Women Who Are At Risk Or May Have Lynch Syndrome

Brief Title

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients

Official Title

A Phase Ib/II Clinical Trial of Nous-209 for Recurrent Neoantigen Immunogenicity and Cancer Immune Interception in Lynch Syndrome

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.

      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 circulating tumor deoxyribonucleic
      acid (DNA) (ctDNA) mutation profiles and ctDNA burden in participants with LS.

      OUTLINE:

      Patients receive GAd20-209-FSPs intramuscularly (IM) on day 1 and MVA-209-FSPs IM at week 8.

      After completion of study treatment, patients are followed up at 6 and 12 months.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Rates of grade 2/3 adverse events and symptom reactivity following vaccination

Secondary Outcome

 Changes in T cell immune profile and T cell receptor (TCR) repertoire in the peripheral blood

Condition

Lynch Syndrome

Intervention

Adenoviral Tumor-specific Neoantigen Priming Vaccine GAd-209-FSP

Study Arms / Comparison Groups

 Prevention (Nous-209 vaccine)
Description:  Patients receive GAd20-209-FSPs IM on day 1 and MVA-209-FSPs IM at week 8.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

45

Start Date

March 23, 2022

Completion Date

November 30, 2025

Primary Completion Date

November 30, 2025

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have a clinical diagnosis of Lynch syndrome (LS) as defined by:

               -  Mutation-positive LS: carriers or obligate carriers (by pedigree) of a pathogenic
                  germline mutation or likely pathogenic mutation in mismatch repair (MMR) genes
                  (MLH1, MSH2/EPCAM, MSH6, or PMS2)

               -  Mutation-negative LS (also known as "Lynch-like syndrome" or "suspected Lynch
                  syndrome): individuals with a personal history of a non-sporadic MMR-deficient
                  premalignant lesion (i.e., colorectal polyp) or a non-sporadic MMR-deficient
                  malignant tumor (where "non-sporadic MMR deficient" is defined by either
                  immunohistochemistry with loss of MLH1, MSH2, MSH6, or PMS2 expression or
                  microsatellite instability (MSI) testing by polymerase chain reaction (PCR) or
                  both, but no evidence of MLH1 promoter methylation in cases with loss of both
                  MLH1 and PMS2, and/or no evidence of BRAF mutation in cases with loss of both
                  MLH1 and PMS2) but germline MMR genetic testing showing either a variant of
                  unknown significance, or mutation negative result, or had declined germline MMR
                  genetic testing

          -  Participants must have no evidence of active or recurrent invasive cancer for 6 months
             prior to screening and must be at least 6 months from any prior cancer-directed
             treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy,
             or radiation)

          -  Participants must have endoscopically accessible distal colon and/or rectal mucosa
             (i.e., participants must have at least part of the descending/sigmoid colon and/or
             rectum intact)

          -  Participants must consent to standard of care surveillance with colonoscopy with
             biopsies every 12 months

          -  Participants must consent to refrain from using aspirin or non-steroidal
             anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX) inhibitors for the duration
             of the trial, except for cardio-preventive aspirin (< 100 mg daily). Individuals
             taking such drugs may not be enrolled unless they are willing to stop the medications
             (and possibly change to alternative non-excluded medications to treat the same
             conditions) no less than 1 month prior to enrollment. Participants will discuss with
             their primary care provider/local provider about the discontinuation of such
             medication(s) and obtain approval prior to stopping any agent

          -  Age >= 18 years. Because no dosing or adverse event (AE) data are currently available
             on the use of Nous-209 in participants < 18 years of age, children are excluded from
             this study but will be eligible for future pediatric trials, if applicable

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

          -  Hemoglobin >= 10 g/dL or hematocrit >= 30 %

          -  Leukocyte count >= 3,500/microliter

          -  Platelet count >= 100,000/microliter

          -  Absolute neutrophil count >= 1,500/microliter

          -  Creatinine clearance (calculated if measured is not available) >= 60 mL/min/1.73 m^2

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =<
             2 times the institutional upper limit of normal (ULN)

          -  Total bilirubin =< 1.5 the ULN; participants with Gilbert's disease may be enrolled
             with higher total bilirubin if their direct bilirubin is =< 1.5 times the ULN

          -  Participants must consent to refrain to receive any other type of vaccination during
             the first 10 weeks of the trial

          -  Participants must consent to refrain from receiving adenoviral-based vaccines for the
             duration of the trial

          -  Willing and able to adhere to the prohibitions and restrictions specified in the final
             approved protocol

          -  The effects of Nous-209 on the developing human fetus at the recommended therapeutic
             dose are unknown. For this reason, women of child-bearing 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. Should a
             woman become pregnant or suspect she is pregnant while participating in this study,
             she should inform her study physician immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Prior receipt of a recombinant adenoviral or MVA vaccine including COVID19 adenovirus
             vaccines within the previous 6 months

          -  Histologically-confirmed high-grade dysplasia or cancer on biopsy at screening

          -  Individuals with active malignancy (excluding non-melanoma skin cancer)

          -  Any serious uncontrolled and/or unstable pre-existing medical disorder (aside from
             malignancy exception above), psychiatric disorder, or other conditions that could
             interfere with participant's safety, obtaining informed consent, or compliance to the
             study procedures

          -  Active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C
             virus (HCV) infection. Participants with laboratory evidence of cleared HBV and HCV
             infection will be permitted

          -  History of organ allograft or other history of immunodeficiency

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to study drug, or excipients

          -  Individuals with a condition requiring systemic treatment with either corticosteroids
             (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within
             14 days of study drug administration. Inhaled or topical steroids and adrenal
             replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of
             active autoimmune disease

          -  Pregnant or breastfeeding or planning to become pregnant within 6 months after the end
             of study. Because there is an unknown but potential risk for adverse events (AEs) in
             nursing infants secondary to treatment of the mother with Nous-209, breastfeeding
             should be discontinued if the mother is treated with Nous-209

          -  Participants may not be receiving any other investigational agents
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Eduardo Vilar-Sanchez, , 

Location Countries

Puerto Rico

Location Countries

Puerto Rico

Administrative Informations


NCT ID

NCT05078866

Organization ID

NCI-2021-10799

Secondary IDs

NCI-2021-10799

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Eduardo Vilar-Sanchez, Principal Investigator, M.D. Anderson Cancer Center


Verification Date

October 2021