Registry Study in MSI/dMMR Solid Tumors

Study Overview
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Brief Summary
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This study is a multi-center, non-interventional, prospective clinical observational study, aiming to evaluate the effectiveness and safety of subsequent treatment in dMMR/MSI solid tumor patients who have never received ICIs under real-world conditions. Particular attention is paid to the efficacy in populations where treatment plans are adjusted based on ctDNA, and potential predictive or prognostic biomarkers are explored.

Detailed Description
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This study plans to enroll patients in the following four cohorts: Cohort A: Initially only receiving PD1/PDL1 monotherapy; Cohort B: Initially receiving simultaneous blockade of PD1/PDL1 and CTLA4; Cohort C: Initially receiving PD1/PDL1 monotherapy combined with chemotherapy or targeted therapy; Cohort D: Initially not using ICIs, receiving other standard treatments for this tumor type To explore the role of ctDNA testing in therapeutic decision-making, patients with the first evaluation of SD in cohort A are divided into two groups: ctDNA testing/intervention group (Group A1) and ctDNA testing/non-intervention group (Group A2). In group A1, if there is no early response to ctDNA, the researchers and the patient will decide to add CTLA4 antibody or other potentially effective treatments after thorough communication. If there is an early response to ctDNA, then continue with PD1/PDL1 monoclonal antibody treatment. Patients in group A2 undergo ctDNA testing, but still continue with PD1/PDL1 monoclonal antibody treatment according to the RECIST v1.1 standard when the first evaluation of SD is made. Meanwhile, explore the role of 1-year ctDNA-MRD in guiding treatment in patients with long-term tumor control, and explore the guiding role of re-biopsy of tumor tissue or ctDNA testing in helping making treatment regimen after progression on ICIs. Number of Subjects: • This study will recruit patients nationwide for data collection over a period of 3 years. The plan is to enroll 100 cases in Cohort A, including 25 cases in Group A1 and 25 cases in Group A2; 30 cases in Cohort B; 30 cases in Cohort C; and 30 cases in Cohort D.

Official Title
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Multi-center, Non-interventional, Prospective Registry Study on the Treatment of Solid Tumors With Mismatch Repair Deficiency or Microsatellite Instability

Conditions
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DMMR Cancer, MSI-H, Solid Tumor

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent form and voluntarily participate in this study; Age ≥ 18 years old; age should also be ≤75 years old in Cohorts B, C, D; Histologically or cytologically confirmed to have a solid malignant tumor and confirmed by immunohistochemistry to be dMMR or confirmed by PCR/NGS to be MSI; The researcher determines that the patient can receive anti-tumor treatment; Have evaluable lesions Exclusion Criteria: Other malignant tumors within 5 years before joining the study, except for cured skin squamous cell carcinoma, basal cell carcinoma, non-muscle invasive bladder cancer, localized low-risk prostate cancer (defined as stage ≤T2a, Gleason score ≤6 points, and prostate cancer diagnosed with PSA ≤10 ng/mL (if measured). Patients who have received radical treatment and have no prostate specific antigen (PSA) biochemical recurrence can participate in this study), cervical/breast carcinoma in situ, and Lynch syndrome; Evidence already exists that the patient is a pregnant or lactating woman; Previous treatment with immune checkpoint inhibitors or T cell co-stimulatory drugs, including but not limited to PD1, CTLA4, LAG3, and other immune checkpoint blockers, therapeutic vaccines, etc.; patients exposed to ICIs in perioperative setting are allowed to be enrolled if disease relapse after more than 6 months since the last dose of ICIs; Other situations deemed by the researcher to be unsuitable for inclusion in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort A<br>Patients will initially receive monotherapy PD1/PDL1 monoclonal antibody therapy. | |
| Cohort B<br>Patients will initially receive dual blockade of both PD1/PDL1 and CTLA4 | |
| Cohort C<br>Patients will initially receive PD1/PDL1 monoclonal antibody combined with chemotherapy or targeted therapy. | |
| Cohort D<br>Patients will receive other standard treatments for this tumor other than ICIs. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) determined by the researchers according to the RECIST 1.1 criteria.. | Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) or death due to any cause. | Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause. | Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose | 
| Overall response rate | Objective response rate (defined as CR+PR) will be reported based on investigator's evaluation. | Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose | 
| Disease control rate | Disease control rate (defined as CR+PR+SD) will be reported based on investigator's evaluation. | Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose | 
| Duration of response | Duration of response (DOR) is defined as the time from the date of the first response to the first objective documentation of radiographic progressive disease (PD) or death due to any cause. | Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose | 
| Treatment-related adverse event | A treatment-related adverse event (TRAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TRAEs were graded using National Cancer Institute (NCI)-CTCAE version 5.0. | Informed consent to 30 days after last dose of treatment |