Preventive Dendritic Cell Vaccination for Lynch Syndrome Carriers

NCT07609901 | Not Yet Recruiting Phase 3

• 2 other identifiers: EU CT 2026-525765-46-002026-525765-46-00
• Study Type: interventional
• Target: 372
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to assess the effect of vaccination with neopeptide-loaded dendritic cells on disease-free survival (DFS) compared to placebo in LS subjects who are known to be carrier of a germline MMR-gene mutation with no signs of disease.

Conditions

Lynch Syndrome

Keywords

Dendritic Cells; Cancer Vaccine; Hereditary Cancer; Lynch Syndrome; Prevention; Neoantigens

Outcome Measures

Primary Outcomes (1)

• Disease-free survival after DC vaccination or placebo

  Defined as time between 1st vaccination until development of mismatch-repair deficient colorectal adenoma, any Lynch-related carcinoma in situ or Lynch-related carcinoma, Lynch-related death, or until follow-up ends, whichever occurs first.

  58.5 months

Secondary Outcomes (4)

• Number of participants with Treatment-Related adverse events as assessed by CTCAE v5.0 (Safety)

  36 months

• Quality of Life Questionnaires

  baseline, week 3, week 28, month 12, month 24, month 36, month 48

• To assess whether neoantigen-specific T cells are induced by the DC vaccine (immunogenicity).

  36 months

• Health economic aspects including QALY

  58.5 months

Study Arms (2)

Arm A: DC vaccination

EXPERIMENTAL

Subjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally

Biological: Arm A: DC vaccination

Arm B: Placebo vaccination

PLACEBO COMPARATOR

Subjects in the placebo vaccination arm will receive a maximum of 2 cycles each consisting of 3 matching placebo injections intranodally

Biological: Arm B: Placebo vaccination

Interventions

Arm A: DC vaccination BIOLOGICAL

Subjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally (3-7x10\^6 DC)

Arm A: DC vaccination

Arm B: Placebo vaccination BIOLOGICAL

Subjects in the placeb vaccination arm will receive a maximum of 2 cycles each consisting of 3 placebo injections intranodally (3-7x10\^6 DC)

Arm B: Placebo vaccination

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• a confirmed gPV in MLH1 or MSH2 and without a prior history of MMR-D cancer.
• a confirmed gPV in MSH6, whether or not they have a history of MMR-D cancer. MSH6 subjects with a history of MMR-D cancer have to be cancer-free for more than 1 year.
• previous surgical treatment may include any resection up to and including hemicolectomy; subjects who have undergone (sub)total colectomy are excluded due to the substantially reduced risk of cancer occurrence.
• aged between 35 and 75 for subjects with gPV in MLH1 and MSH2; and aged between 40 and 75 for subjects with gPV in MSH6.
• Lynch syndrome subjects without clinical signs of disease.
• Lynch syndrome subjects without prior treatment for LS-associated cancer, except for MSH6 subjects who are \>1 year disease-free and whose prior surgical treatment did not include subtotal colectomy.
• Routine surveillance colonoscopy must be performed within 16 weeks prior to start of study, to exclude (pre)malignancy.
• HLA-A02.01 genotype
• Adequate hematologic, renal, and liver function as defined by laboratory values: WBC \>3.0\^109/l, lymphocytes \>0.8\^109/l, platelets \>100\^109/l, haemoglobin \>7,0 mmol/l (9.0 g/dl), estimated glomerular filtration rate \> 45 ml/min/1.73m2, AST/ALT \<3 x ULN, serum crea¬tinine \<150 µmol/l, serum bilirubin \<1.5 x ULN (exception: Gilbert's syndrome is permitted).
• WHO performance status of 0 or 1
• No concomitant use of immunosuppressive drugs orally or intravenously. Topical and intranasal steroids are permitted.
• No uncontrolled infectious disease, i.e., negative testing for HIV, Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and syphilis (Treponema Pallidum Hemagglutination Assay (TPHA)).
• No autoimmune disease such as, but not limited to, inflammatory bowel disease, multiple sclerosis, and lupus. Subjects with type 1 diabetes mellitus, hypothyroidism after autoimmune thyroiditis and skin disorders are not excluded.
• No serious (bleeding and clotting) condition that may interfere with safe leukapheresis.
• No pregnant or lactating women. hCG tests will be performed regularly during the trial to confirm absence of pregnancy.

You may not qualify if:

• Individuals with a history of malignancy in the past. Allowed malignancies are adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, carcinoma in situ (e.g., DCIS/LCIS/cervical CIS), papillary thyroid carcinoma, and low-risk prostate carcinoma; all locally resected with negative surgical margins and not treated with systemic therapy.
• Organ allografts.
• Known allergy to shellfish.
• Inability to understand and communicate in Dutch.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Dutch National Health Care Institute: collaborator

Study Sites (1)

Radboudumc

Nijmegen, Gelderland, Netherlands

Location

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Arm A: Vaccination with neopeptide-loaded dendritic cells Arm B: Vaccination with placebo

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: May 27, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2032
• Study Completion (Estimated): October 1, 2032
• Last Updated: May 27, 2026

Record last verified: 2026-05

Locations

NL (1)