First in Human Pilot Study to Assess the Safety and Efficacy of Dendritic Cells Loaded With Frameshift Derived Neopeptides for the Prevention of Cancer in of Lynch Syndrome Carriers

NCT07163403 | Recruiting Phase 1 DMC

• 1 other identifier: 2025-521109-42-00
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Tha aim of this clinical trial is to evaluate safety and tolerability of autologous peripheral blood differentiated and matured adult dendritic cells. Immunogenicity of the prduct(DC-DELAY) will be evaluated also.

Conditions

Lynch Syndrome

Outcome Measures

Primary Outcomes (2)

• Proportion of participants with grade 3-4 related adverse events for 12 months following the first immunization.

  To evaluate the safety and tolerability of autologous peripheral blood differentiated and matured adult dendritic cells loaded with frameshift derived neopeptides (DC-DELAY) in LS carriers.

  the first 12 month after the last inmunization

• Proportion of participants with specific frameshift-derived neoantigens immune response induced by DC-DELAY as measured in peripheral blood by enzyme-linked immune absorbent spot(ELISpot) assay at week 12.

  To evaluate specific frameshift-derived neoantigens immunogenicity of DC-DELAY in LS carriers at week 12. NOTE: Immune response will be defined as T-cell reactivity to at least 1 out of 4 of the pools.

  At week 12.

Secondary Outcomes (7)

• Proportion of participants with early immune response induced by DC-DELAY as measured inperipheral blood by ELISpot assay at week 6.

  Week 6

• Proportion of participants with long term immune response induced by DC-DELAY as measured in peripheral blood by ELISpot assay at months 6, 12 and 24.

  Month 6, 12 and 24.

• Proportion of participants with immune response induced by DC-DELAY as measured in the normal colonic mucosa at month 12.

  Month 12

• Proportion of participants with mismatch repair deficient colorectal adenomas, advanced neoplasia and/or carcinoma throughout the study duration.

  Month 12 and month 36

• Proportion of participants with LS-related carcinomas throughout the study duration (36 months).

  Week 12 and month 36

Study Arms (1)

Single Arm

EXPERIMENTAL

Patients with Lynch Syndrome which will recieve their own dendritic cells to evaluate safety and tolerability

Biological: Autologous Tolerogenic Dendritic cells

Interventions

Autologous Tolerogenic Dendritic cells BIOLOGICAL

Autologous peripheral blood differentiated and matured adult dendritic cells loaded with Frameshift-derived neopeptides (FSDN) (DC-DELAY). Eligible participants will receive six intradermal immunizations of DC-DELAY at week 0, 2, 4, 6, 8 and 10.

Single Arm

Eligibility Criteria

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

You may qualify if:

• Individuals that are carriers of a pathogenic or likely pathogenic germline variant in one of the mismatch repair genes (MLH1, MSH2, MSH6).
• Participants must have no evidence of active or previous invasive cancer.
• Participants must have endoscopically accessible colon.
• Participants must consent to follow the standard of care surveillance with colonoscopy and biopsies every 1-2 years.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Karnofsky ≥70%).
• Haemoglobin ≥10 g/dL or haematocrit ≥30%; Leukocyte count ≥3.0x109/l; Platelet count ≥100x109/l; Absolute neutrophil count ≥1.5x109/l; Absolut lymphocyte count ≥0.8x109/l.
• Creatinine clearance (calculated if measured is not available) ≥60mL/min/1.73m2.
• 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.
• Written informed consent.

You may not qualify if:

• Individuals that are carriers of a pathogenic or likely pathogenic germline variant in PMS2.
• Individuals with active malignancy or previous malignancy (excluding non-melanoma skin cancer)
• Participants who cannot be removed from their baseline medication for the duration of the trial to administer the investigational treatment. This includes the daily use of \>100 mg aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX) inhibitors.
• 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.
• Patients with active systemic bacterial, viral or fungal infections or known to have human immunodeficiency virus (HIV) or to test positive for HIV antibody at screening.
• Positive hepatitis B surface antigen or hepatitis C antibody tests at screening.
• History of organ allograft or other history of immunodeficiency
• Individuals with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications.
• Pregnant or breastfeeding or planning to become pregnant during the first year after the completion of the study treatment.
• Men attempting or planning to conceive children during the first year after the completion of the study treatment.
• Participants unable to refrain to receive any type of vaccination during the first 12 weeks of the trial.
• Impossibility to proceed to the leukapheresis (e.g. absence of peripheral venous access).
• Any other problem that according to the investigator could interfere with the evaluation of the objectives

Sponsors & Collaborators

• Fundacion Clinic per a la Recerca Biomédica: lead

Study Sites (1)

Laura Burunat

Barcelona, Barcelona, 08036, Spain

RECRUITING

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

Central Study Contacts

Laura Burunat, Graduate

CONTACT

0034 932275400; burunat@recerca.clinic.cat

Thomas Walle, Doctor of Medicine

CONTACT

0034932275400; WALLE@recerca.clinic.cat

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: September 9, 2025
• Study Start: September 4, 2025
• Primary Completion (Estimated): September 20, 2028
• Study Completion (Estimated): September 20, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-02

Locations

ES (1)