Clinical Study of MSH2-/- Tumor Cell Vaccines for Advanced pMMR Colorectal Cancer Patients

NCT07510308 | Recruiting Phase 1

• 1 other identifier: 2025-2583
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to evaluate the safety and tolerability of an MSH2-/- tumor cell vaccine and to explore its preliminary antitumor activity and immunogenicity in adults with advanced proficient mismatch repair (pMMR) colorectal cancer who have failed, are intolerant of, or decline standard systemic therapies at West China Hospital, Sichuan University. The main objectives are to determine the incidence of dose-limiting toxicities (DLTs) and other treatment-emergent adverse events (TEAEs) related to the vaccine (n/N, %, graded per NCI CTCAE v5.0), to assess preliminary antitumor activity (objective response per RECIST v1.1, progression-free survival, and overall survival), and to characterize the vaccine's immunogenicity profile. This study using a 3+3 dose-escalation design with three dose levels of the MSH2-/- tumor cell vaccine (1×10\^7, 2.5×10\^7, and 5×10\^7 cells per dose), manufactured under GMP conditions and administered by intradermal injection. Each participant will receive four induction vaccinations (three doses every 2 weeks and a fourth dose 1 month after the third), followed by up to eight booster doses every 4 weeks based on tumor response. Participants will undergo protocol-specified safety monitoring with clinical assessments, laboratory tests, and documentation of all AEs/SAEs, and tumor response will be evaluated regularly by imaging per RECIST v1.1. After treatment completion or discontinuation, participants will enter safety and long-term follow-up for disease status and survival.

Conditions

pMMR/MSS Advanced Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0)

  DLTs are defined as treatment-related adverse events (graded according to NCI-CTCAE v5.0) occurring during the DLT observation period that meet specific protocol-defined criteria for hematologic and non-hematologic toxicity.

  From the first dose through 14 days following the third dose.

• Number of Participants Experienced Treatment-emergent adverse events (TEAEs) according to NCI CTCAE V5.0

  Treatment-emergent adverse events (TEAEs) related to the study drug (including definitely related, probably related, and possibly related), graded according to NCI CTCAE V5.0

  12 months

Secondary Outcomes (4)

• Number of participants achieving complete response (CR) According to Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1

  12 months

• Number of participants achieving partial response (PR) According to RECIST 1.1

  12 months

• Progression Free Survival (PFS) According to RECIST 1.1

  6 months

• Overall Survival(OS)

  12 months

Other Outcomes (1)

• Assessment of Tumor Immune Microenvironment Changes

  12 months

Study Arms (3)

MSH2-/- Tumor Cell Vaccine (Low Dose )

EXPERIMENTAL

Participants receive the MSH2-/- tumor cell vaccine at a dose of 1×10\^7 inactivated tumor cells.

Biological: Low Dose MSH2-/- tumor cell vaccine

MSH2-/- Tumor Cell Vaccine (Medium Dose)

EXPERIMENTAL

Participants receive the MSH2-/- tumor cell vaccine at a dose of 2.5×10\^7 inactivated tumor cells.

Biological: Medium Dose MSH2-/- tumor cell vaccine

MSH2-/- Tumor Cell Vaccine (High Dose)

EXPERIMENTAL

Participants receive the MSH2-/- tumor cell vaccine at a dose of 5×10\^7 inactivated tumor cells.

Biological: High dose MSH2-/- tumor cell vaccine

Interventions

Low Dose MSH2-/- tumor cell vaccine BIOLOGICAL

Participants were assigned to receive the MSH2-/- tumor cell vaccine in the number of 1x10e7 tumor cells per dose.

MSH2-/- Tumor Cell Vaccine (Low Dose )

Medium Dose MSH2-/- tumor cell vaccine BIOLOGICAL

Patients will receive the MSH2-/- tumor cell vaccine in the number of 2.5x10e7 tumor cells per dose.

MSH2-/- Tumor Cell Vaccine (Medium Dose)

High dose MSH2-/- tumor cell vaccine BIOLOGICAL

Patients will receive the MSH2-/- tumor cell vaccine in the number of 5x10e7 tumor cells per dose.

MSH2-/- Tumor Cell Vaccine (High Dose)

Eligibility Criteria

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

You may qualify if:

• Patients aged 18 to 75 years at the time of acquisition informed consent form.
• Patients with histologically or cytologically confirmed pMMR colorectal cancer based on molecular typing, who have experienced failure of, are intolerant to, or refuse standard therapy.
• For patients with RAS/BRAF wild-type disease who are eligible for targeted therapy, enrollment is permitted only after they have previously received standard regimens containing an anti-EGFR monoclonal antibody or an anti-VEGF monoclonal antibody and subsequently experienced disease progression.
• For patients with a BRAF V600E mutation, enrollment is permitted only after failure of prior treatment with a regimen containing a BRAF inhibitor in combination with chemotherapy.
• For patients who do not meet the above molecular criteria, enrollment is permitted only after failure of at least two prior lines of systemic chemotherapy, including platinum-based agents.
• The presence of at least one measurable or evaluable lesion according to RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status score: 0-2.
• Predicted survival time ≥3 months.
• The main organs are functioning well and the following requirements are met within 7 days before receiving treatment:
• ① Hemoglobin (HGB) ≥80 g/L (no blood transfusion within 14 days); Absolute neutrophil count (ANC) \>1.5×109/L; White blood cell count ≥3.0×109/L; Platelet count (PLT) ≥80×109/L;
• ② Total bilirubin ≤1.5× upper limit of normal value (ULN); Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5×ULN; If there was liver metastasis, ALT or AST≤5×ULN;
• ③ Creatinine (SCr) ≤1.5×ULN or creatinine clearance (CRCI) estimated by Cockcroft-Gault formula ≥60 mL/min;
• ④ Prothrombin time (PT), international normalized ratio (INR) ≤1.5×ULN (unless anticoagulation with warfarin);
• ⑤ Cardiac function: left ventricular ejection fraction ≥50%. QTcF interval ≤450 ms.
• Men of childbearing potential and women of childbearing age voluntarily use effective contraceptive methods (e.g., condoms, intrauterine devices, spermicides) from the time of signing the informed form until 6 months after the completion of vaccination, and contraceptive use is not allowed. Female cancer patients who have a negative pregnancy test and agree not to breastfeed during the study and for at least 18 months after receipt of the trial vaccine;

You may not qualify if:

• The patient has a history of other tumors in the past, except for the history of malignant tumors that have been cured and have not recurred within 5 years before screening, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical cancer in situ, and intramucosal cancer of the gastrointestinal tract, which the investigator considers to be eligible for enrollment.
• Have any uncontrolled clinical diseases (e.g., diseases of the respiratory system, circulatory system, digestive system, nervous system, hematologic system, urogenital system, endocrine system) or psychiatric or other major medical condition that the investigator considers to interfere with the provision of informed consent, to interfere with the interpretation of the trial results, to pose a risk to the study participants, or to otherwise interfere with the achievement of the study objectives.
• Have any active autoimmune disease or a history of autoimmune disease. Participants with asthma for which medical intervention with bronchodilators was required could not be included.
• Allergy to the trial drug (including any excipients). Previous history of severe allergy to any drug, food or vaccination, such as anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, local allergic necrosis reaction (Arthus reaction), etc.
• There are contraindications to subcutaneous injection.
• Received prior antitumor therapeutic vaccine or cellular immunotherapy.
• Participated in other drug or device clinical trials 4 weeks before screening.
• Study participants on systemic therapy with corticosteroids (\>10 mg/ day of prednisone or equivalent doses of other glucocorticoids) or other immunosuppressive agents within 14 days before the first dose of vaccine. Inhaled or topical steroids and adrenal hormone replacement at a therapeutic dose of prednisone of 10 mg or less per day were allowed in the absence of active autoimmune disease.
• Before the first dose of the study drug. Any toxic effects from previous antineoplastic therapy have not recovered to NCI CTCAE grade 5.0 ≤1 (any degree of alopecia, other than grade 2 previous platinum-based treatment-related neuropathy).
• Has active infection including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
• Have a history of substance abuse or known medical, psychological, or social conditions such as alcohol or drug abuse.
• Have received any vaccine within 30 days before receiving the study vaccine or plan to receive any vaccine other than the study vaccine during the study.
• The presence of any other factor that was deemed by the investigator to preclude study participant entry into the trial or that study participant had any medical condition that could interfere with the assessment of the safety or efficacy of the study treatment.
• Study participants who were unwilling or unable to comply with study requirements.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (2)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, China

RECRUITING

Related Publications (13)

• Pang K, Sun P, Liu X, Yang D, Zhao P, Huang Y, Cao S, Gao Y, Chen G, Yu H, Duan L, Yang Y, Zhang Z. Development of the rationale of a personalized cancer vaccine based on the in situ vaccine effect of radiotherapy: a mechanistic study of the POLARSTAR trial. Cancer Immunol Immunother. 2025 Nov 12;74(12):369. doi: 10.1007/s00262-025-04229-3.

  PMID: 41222702 BACKGROUND

• De Marco L, Micarelli E, Panula J, Nikkola J, Moilanen L, Annala M, Harkonen J, Hokkanen KE, D'Alise AM, Pylvanainen K, Peltomaki PT, Ahtiainen M, Bohm J, Mecklin JP, Scarselli E, Seppala TT. NOUS-209 off-the-shelf immunotherapy has the potential to hit primary and metachronous colorectal and urothelial cancer in Lynch syndrome. Mol Cancer Ther. 2025 Nov 13. doi: 10.1158/1535-7163.MCT-25-0864. Online ahead of print.

  PMID: 41232028 BACKGROUND

• Li J, Wang P. Advances in Cancer Vaccines for Digestive System Cancers: A Systematic Analysis of Clinical Trials. Cancer Manag Res. 2025 Nov 11;17:2691-2703. doi: 10.2147/CMAR.S561298. eCollection 2025.

  PMID: 41245584 BACKGROUND

• Passardi A, Sullo FG, Bittoni A, Matteucci L, De Rosa F, Bulgarelli J, Tazzari M, Petrini M, Scarpi E, Testoni S, Miserocchi A, Tartagni O, Zani C, Iaia ML, Toma I, Viola MG, Mita MT, Tamburini E, Ridolfi L. CombiCoR-Vax trial: study protocol for a phase II, single-arm, multicenter trial of sequential pembrolizumab plus dendritic cell vaccine followed by trifluridine/tipiracil and bevacizumab in refractory microsatellite-stable metastatic colorectal cancer. BMC Cancer. 2025 Nov 22;25(1):1921. doi: 10.1186/s12885-025-15371-7.

  PMID: 41275134 BACKGROUND

• Karimzadeh F, Heidari R, Lamooki FM, Soureshjani EH, Aziz S, Mirzaei SA. Design of a multi-epitope vaccine against intestinal parasites associated with colorectal cancer using immunoinformatics approaches. Sci Rep. 2025 Dec 8;16(1):1487. doi: 10.1038/s41598-025-31713-8.

  PMID: 41360964 BACKGROUND

• D'Alise AM, Willis J, Duzagac F, Hall MJ, Cruz-Correa M, Idos GE, Thirumurthi S, Ballester V, Leoni G, Garzia I, Antonucci L, De Marco L, Micarelli E, Deng N, Secli L, Gogov S, Dong W, Jack Lee J, Bowen CM, Vornik LA, Garcia-Gonzalez A, Reyes-Uribe L, Richmond E, Umar A, Brown PH, Sinha KM, Rodriguez LM, Scarselli E, Vilar E. Nous-209 neoantigen vaccine for cancer prevention in Lynch syndrome carriers: a phase 1b/2 trial. Nat Med. 2026 Mar;32(3):1002-1011. doi: 10.1038/s41591-025-04182-9. Epub 2026 Jan 16.

  PMID: 41545594 BACKGROUND

• Huang J, Tian G. Immunotherapy in advanced colorectal cancer: Current landscape, mechanisms, challenges, and future directions. J Oncol Pharm Pract. 2026 Jan 22:10781552251414845. doi: 10.1177/10781552251414845. Online ahead of print.

  PMID: 41571235 BACKGROUND

• Hamdan F, Gandolfi S, D'Alessio F, Giannoula Y, Kolikova J, Fusciello M, Zaghen E, Napolano A, Russo S, Izci O, Bottega P, Chiaro J, Alanen KM, Antignani G, Feodoroff M, Stigzelius V, Sakalauskaite M, Sandberg J, Nieminen AI, Zambrano N, Eriksson O, Mustjoki S, Seppala TT, Gronholm M, Cerullo V. Leveraging glucan-induced trained immunity for the epigenetic and metabolic rewiring of macrophages to enhance colorectal cancer vaccine response. Nat Commun. 2026 Jan 28;17(1):1757. doi: 10.1038/s41467-026-68466-5.

  PMID: 41605920 BACKGROUND

• Yang Q, Shi X, Yang K, Gao Q, Cao Y, Huang Y, Chen L, Bao S, Xu L, Reis RL, Kundu SC, Xu H, Xiao B. A manganese-based nanoplatform leveraging chemodynamic and adjuvant effects for in situ vaccination against colorectal cancer. Biomaterials. 2026 Feb 18;331:124085. doi: 10.1016/j.biomaterials.2026.124085. Online ahead of print.

  PMID: 41723903 BACKGROUND

• Wang D, Zhang H, Xiang T, Wang G. Clinical Application of Adaptive Immune Therapy in MSS Colorectal Cancer Patients. Front Immunol. 2021 Oct 13;12:762341. doi: 10.3389/fimmu.2021.762341. eCollection 2021.

  PMID: 34721435 BACKGROUND

• Keivany MR, Shojae E, Besharatloo M, Latifi H, Barjasteh AH. Advances in immunotherapy for colorectal cancer: overcoming resistance in mismatch repair-proficient tumors. Cancer Cell Int. 2026 Feb 19. doi: 10.1186/s12935-026-04177-7. Online ahead of print.

  PMID: 41715188 BACKGROUND

• Bolivar AM, Duzagac F, Sinha KM, Vilar E. Advances in vaccine development for cancer prevention and treatment in Lynch Syndrome. Mol Aspects Med. 2023 Oct;93:101204. doi: 10.1016/j.mam.2023.101204. Epub 2023 Jul 19.

  PMID: 37478804 BACKGROUND

• Tang TY, Colbert Maresso K, Ngeow J, Vilar E, Yap TA. Germline Mutations as Cancer Drug Targets. Cancer Discov. 2025 Nov 3;15(11):2213-2234. doi: 10.1158/2159-8290.CD-24-1241.

  PMID: 41178351 BACKGROUND

Study Officials

• Xingchen Peng, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingchen Peng, Ph.D

CONTACT

+8618980606753; pxx2014@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 17, 2026
• First Posted: April 3, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)