MSH2-/- tumor cell vaccine for advanced pMMR (MSS) colorectal cancer

A Clinical Trial Evaluating the Safety, Tolerability, and Preliminary Antitumor Activity of MSH2-/- Tumor Cell Vaccines in Patients With Advanced pMMR Colorectal Cancer.

This early-phase test will see if an MSH2-/- tumor cell vaccine is safe and can stimulate an immune response and anti-tumor activity in adults with advanced pMMR (MSS) colorectal cancer who have exhausted or declined standard treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: West China Hospital (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone
• Locations: 2 sites (Chengdu, Sichuan and 1 other locations)
• Trial ID: NCT07510308 on ClinicalTrials.gov

What this trial studies

This single-center Phase 1, open-label trial uses a 3+3 dose-escalation design to test three intradermal vaccine dose levels (1×10^7, 2.5×10^7, and 5×10^7 cells per dose) manufactured under GMP at West China Hospital. The primary focus is safety and tolerability, with dose-limiting toxicities (DLTs) and treatment-emergent adverse events graded per NCI CTCAE v5.0 as key endpoints. Secondary and exploratory measures include preliminary antitumor activity by RECIST v1.1 (objective response, progression-free survival, overall survival) and detailed immunogenicity profiling. Eligible adults aged 18–75 must have histologically confirmed pMMR colorectal cancer and have failed, been intolerant of, or declined standard systemic therapies, with certain molecular-treatment history requirements applied.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 with histologically confirmed pMMR (MSS) advanced colorectal cancer who have progressed on or cannot tolerate standard systemic therapies or who decline those options and who can attend study visits at West China Hospital in Chengdu.

Not a fit: Patients with mismatch repair–deficient (dMMR/MSI‑high) tumors, those still eligible for standard targeted regimens per their molecular profile, or people unable to travel to the study site are unlikely to receive benefit from this trial.

Why it matters

Potential benefit: If successful, the vaccine could prime the immune system to recognize and slow or shrink pMMR colorectal tumors that typically respond poorly to current immunotherapies.

How similar studies have performed: Tumor-cell vaccine approaches are relatively novel with mixed early-phase results and limited prior success in pMMR colorectal cancer, although some vaccine platforms have demonstrated immunogenicity in small trials.

Eligibility criteria

Inclusion Criteria:

1. Patients aged 18 to 75 years at the time of acquisition informed consent form.
2. 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.

   1. 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.
   2. 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.
   3. 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.
3. The presence of at least one measurable or evaluable lesion according to RECIST v1.1 criteria.
4. Eastern Cooperative Oncology Group (ECOG) performance status score: 0-2.
5. Predicted survival time ≥3 months.
6. 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.
7. 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;
8. The washout period of previous anti-tumor therapy should be at least 4 weeks, and the washout period of molecular targeted drugs should be at least 5 half-lives. Palliative radiotherapy needs to have been completed for at least 2 weeks; Chest radiation therapy needed to have been completed for at least 3 months, and major surgery needed to have been completed with at least 4 weeks of recovery.

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. 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.
5. There are contraindications to subcutaneous injection.
6. Received prior antitumor therapeutic vaccine or cellular immunotherapy.
7. Participated in other drug or device clinical trials 4 weeks before screening.
8. 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.
9. 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).
10. Has active infection including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
11. Have a history of substance abuse or known medical, psychological, or social conditions such as alcohol or drug abuse.
12. 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.
13. 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.
14. Study participants who were unwilling or unable to comply with study requirements.

Where this trial is running

Chengdu, Sichuan and 1 other locations

• West China Hospital, Sichuan University — Chengdu, Sichuan, China (RECRUITING)
• West China Hospital, Sichuan University — Chengdu, Sichuan, China (RECRUITING)

Study contacts

• Principal investigator: Xingchen Peng, MD — West China Hospital
• Study coordinator: Xingchen Peng, Ph.D

Conditions: pMMR/MSS Advanced Colorectal Cancer