Lynch SyndromePhase 3PROTECT-LynchNCT07609901
Preventive Dendritic Cell Vaccination for Lynch Syndrome Carriers
A Phase 3 study testing Arm A: DC vaccination in people with Lynch Syndrome, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Lynch Syndrome
- What is being tested?
- Arm A: DC vaccination
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 372 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Oct 2026to 1 Oct 2032
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 19Show fewer
- 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.
- No Women Of Child-Bearing Potential (WOCBP) or male partners of WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for up to 8 weeks after the last administration of the treatment. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea > 12 consecutive months].
- Subjects must have absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions must be discussed with the subject before registration in the trial.
- Expected adequacy of follow-up.
- Written informed consent.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site
Radboudumc
Nijmegen, Gelderland
Jolanda de Vries, Prof. dr., 0243617600, dcvaccinatie.til@radboudumc.nl
About this study
Official title: Prevention of Tumour Occurrence by Targeting Emergent Cancer Neoantigens Through Therapeutic Vaccination in Lynch Syndrome Carriers: a Phase III Clinical Trial.
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.
Read the detailed description
A phase III, multicentre, randomised, double-blind, placebo-controlled trial evaluating disease-free survival after vaccination with with neopeptide-loaded dendritic cells or placebo in LS subjects aged 35-75 who are confirmed to carry a germline MMR-gene mutation in MLH1, MSH2 or MSH6 without clinical signs of disease. Participants will be treated for 6 months + 4 weeks, with an additional maximum follow-up of 51.5 months (total study duration 58.5 months).
- Conditions
- Lynch Syndrome
- Being tested
- Arm A: DC vaccination, Arm B: Placebo vaccination
- Keywords
- Dendritic Cells, Cancer Vaccine, Hereditary Cancer, Lynch Syndrome, Prevention, Neoantigens
- Medical subject headings
- Colorectal Neoplasms, Hereditary Nonpolyposis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm A: DC vaccinationBiological
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 B: Placebo vaccinationBiological
Subjects in the placeb vaccination arm will receive a maximum of 2 cycles each consisting of 3 placebo injections intranodally (3-7x10^6 DC)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Biological: Arm B: Placebo vaccination |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 58.5 months
Secondary outcomes (4)
Number of participants with Treatment-Related adverse events as assessed by CTCAE v5.0 (Safety)
Measured: 36 months
Quality of Life Questionnaires
To evaluate whether LS subjects quality of life differs between DC vaccinated and placebo vaccinated groups. Defined as patient's self-perceived physical, psychological and social well-being in relation to their health status, assessed using questionnaires.
Measured: 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).
Immunogenicity will be assessed by the percentage of participants showing a neo-antigen-specific T cell response, defined by the expansion of T cells that recognize tumor antigens and demonstrate effector functions. Non-responders are those with no T cell expansion or insufficient immune activity.
Measured: 36 months
Health economic aspects including QALY
The primary objective of the analysis is to determine the cost-effectiveness of DC vaccination compared with standard surveillance in patients with LS, expressed as cost per quality-adjusted life year (QALY) gained and incremental net monetary benefit (iNMB) from a societal perspective, over both the trial timeframe (empirical) and the long term timeframe (modelling).
Measured: 58.5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Oct 2032 (estimated)
- Study completion1 Oct 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lynch SyndromeStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Arm A: Vaccination with neopeptide-loaded dendritic cells Arm B: Vaccination with placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 372 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch National Health Care Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07609901
- Sponsor's protocol ID
- EU CT 2026-525765-46-00
- Other IDs
- 2026-525765-46-00
- Acronym
- PROTECT-Lynch
- Status last verified
- May 2026
- First submitted
- 20 May 2026
- Last updated
- 27 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Tumour Occurrence by Targeting Emergent Cancer Neoantigens Through Therapeutic Vaccination in Lynch Syndrome Carriers: a Phase III Clinical Trial.
- ClinicalTrials.gov ID
- NCT07609901
- Acronym / sponsor ID
- PROTECT-Lynch / EU CT 2026-525765-46-00
- Conditions
- Lynch Syndrome
- Keywords
- Dendritic Cells, Cancer Vaccine, Hereditary Cancer, Lynch Syndrome, Prevention, Neoantigens
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 372 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Dutch National Health Care Institute
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Oct 2032 (estimated)
- Study completion
- 1 Oct 2032 (estimated)
- First posted
- 27 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A phase III, multicentre, randomised, double-blind, placebo-controlled trial evaluating disease-free survival after vaccination with with neopeptide-loaded dendritic cells or placebo in LS subjects aged 35-75 who are confirmed to carry a germline MMR-gene mutation in MLH1, MSH2 or MSH6 without clinical signs of disease. Participants will be treated for 6 months + 4 weeks, with an additional maximum follow-up of 51.5 months (total study duration 58.5 months).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Arm A: Vaccination with neopeptide-loaded dendritic cells Arm B: Vaccination with placebo
| Arm | Type | Receives |
|---|---|---|
| Arm A: DC vaccination | Experimental | Biological: Arm A: DC vaccinationSubjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally |
| Arm B: Placebo vaccination | Placebo comparator | Biological: Arm B: Placebo vaccinationSubjects in the placebo vaccination arm will receive a maximum of 2 cycles each consisting of 3 matching placebo injections intranodally |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arm A: DC vaccinationSubjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally (3-7x10^6 DC) | Biological | Arm A: DC vaccination |
| Arm B: Placebo vaccinationSubjects in the placeb vaccination arm will receive a maximum of 2 cycles each consisting of 3 placebo injections intranodally (3-7x10^6 DC) | Biological | Arm B: Placebo vaccination |
Primary outcome
Disease-free survival after DC vaccination or placebo
Time frame: 58.5 months
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.
4 secondary outcomes
Number of participants with Treatment-Related adverse events as assessed by CTCAE v5.0 (Safety)
Time frame: 36 months
Quality of Life Questionnaires
Time frame: 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).
Time frame: 36 months
Health economic aspects including QALY
Time frame: 58.5 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Arm A: DC vaccination in people with Lynch Syndrome, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival after DC vaccination or placebo (time frame: 58.5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.