Immune Checkpoint Inhibitors for Organ Preservation in Non-metastatic dMMR/MSI-H Gastric or Colon Cancers
NCT Number: NCT06580574
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Gastric Cancer|Colon Cancer|MSI-H|DMMR Cancer
Interventions: DRUG: PD1/PDL1 antibody monotherapy, up to 24 weeks|COMBINATION_PRODUCT: Intensive immunotherapy plus anti-VEGF treatment, up to 24 weeks|PROCEDURE: Radical surgery
Sponsor: Peking University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 38
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-13
Completion Date: 2029-06-01
Locations: Beijing Cancer Hospital, Beijing, Beijing, 100142, China

Summary:
This study intends to explore the role of PD1/PDL1 antibody with selective combination of Sintilimab, IBI310 and Lenvatinib in organ preservation in non-metastatic dMMR/MSI-H gastric or colon cancers with mismatch repair deficiency or high microsatellite instability

Primary Outcome Measures: Organ preservation rate, The rate of patients who achieved cCR or near-cCR and did not undergo surgery after completion of established therapy, assessed among all patients who completed established therapy., The status of cCR or near-cCR and the possibility of organ preservation will be evaluated after completion of PD1/PDL1 antibody monotherapy, 12 weeks after Sintilimab, IBI310 and Lenvatinib, and 24 weeks after Sintilimab, IBI310 and Lenvatinib
Secondary Outcome Measures: Organ preservation rate after completion of PD1/PDL1 antibody monotherapy, The rate of patients who achieve cCR or near-cCR and do not undergo surgery after completion of PD1/PDL1 antibody monotherapy, assessed among all patients who completed PD1/PDL1 antibody monotherapy, The status of cCR or near-cCR and the possibility of organ preservation will be evaluated after completion of PD1/PDL1 antibody monotherapy, an average of 24 weeks|Organ preservation rate after completion of selective combination of Sintilimab, IBI310 and Lenvatinib, The rate of patients who achieved cCR or near-cCR and did not undergo surgery after completion of selective combination of Sintilimab, IBI310 and Lenvatinib, assessed among all patients who do not achieve cCR or near-cCR after PD1/PDL1 antibody monotherapy, and all patients who achieve cCR or near-cCR after PD1/PDL1 antibody monotherapy but have disease progression during follow-up, The status of cCR or near-cCR and the possibility of organ preservation will be evaluated 12 weeks and 24 weeks after Sintilimab, IBI310 and Lenvatinib|Objective response rate of selective combination of Sintilimab, IBI310 and Lenvatinib, Objective response rate (defined as CR+PR) will be reported based on investigator's evaluation according to RECIST 1.1, Baseline up to withdrawal of consent, progressive disease, unacceptable toxicity, or surgery (whichever occurs first), up to 8 years|Disease control rate of selective combination of Sintilimab, IBI310 and Lenvatinib, Disease control rate (defined as CR+PR+SD) will be reported based on investigator's evaluation according to RECIST 1.1, Baseline up to withdrawal of consent, progressive disease, unacceptable toxicity, or surgery (whichever occurs first), up to 8 years|3 year organ preservation rate, Rate of 3 year surgery-free survival, From first dose of PD1/PDL1 antibody until the date of surgery, assessed up to 3 years|3 year disease free survival rate, Rate of 3 year disease free survival, From first dose of PD1/PDL1 antibody until disease progression (local or distant), secondary tumor or death (whichever occurs first), assessed up to 3 years|3 year overall survival rate, Rate of 3 year overall survival, From first dose of PD1/PDL1 antibody until death, assessed up to 3 years|5 year overall survival rate, Rate of 5 year overall survival, From first dose of PD1/PDL1 antibody until death, assessed up to 5 years|3 year local recurrence free survival rate, Rate of 3 year local recurrence free survival, From first dose of PD1/PDL1 antibody until first local failure or death (whichever occurs first), assessed up to 3 years|3 year distant metastasis free survival rate, Rate of 3 year distant metastasis free survival, From first dose of PD1/PDL1 antibody until distant metastasis or death (whichever occurs first), assessed up to 3 years|3 year surgery free survival rate, Rate of 3 year surgery free survival, From first dose of PD1/PDL1 antibody until radical surgery or death (whichever occurs first), assessed up to 3 years|Treatment-related adverse event of combination of Sintilimab, IBI310 and Lenvatinib, 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., From first dose of Sintilimab, IBI310 and Lenvatinib to 30 days after last dose of treatment.|Quality of life of combination of Sintilimab, IBI310 and Lenvatinib for gastric cancer patients, Quality of life will be evaluated using EORTC QLQ-C30 and QLQ-STO22., From first dose of PD1/PDL1 antibody until death, assessed up to 8 years|Quality of life of combination of Sintilimab, IBI310 and Lenvatinib for colon cancer patients, Quality of life will be evaluated using EORTC QLQ-C30 and EORTC QLQ-CR29., From first dose of PD1/PDL1 antibody until death, assessed up to 8 years|Rate of complications, Rate of complications in perioperative period, From 7 days before surgery to 12 days after surgey|Rate of mortality, Rate of mortality in perioperative period, From 7 days before surgery to 12 days after surgey
Other Outcome Measures: Exploratory outcome-Proportion and location of different immune cell subsets at baseline and during treatment associated with cCR or near cCR, Proportion and location of different immune cell subsets will be assessed by single-cell sequencing, immunohistochemistry, and multiplex fluorescence immunohistochemistry., From baseline to withdrawal of consent or death (whichever occurs first), up to 8 years|Exploratory outcome-Tumor gene alterations associated with cCR or near cCR, Tumor gene alterations will be assessed by whole exome sequencing using tissue or blood samples., From baseline to withdrawal of consent or death (whichever occurs first), up to 8 years|Exploratory outcome-Baseline clinical and pathological characteristics associated with cCR or near cCR, Baseline clinical characteristics include age of onset, gender, family history, pathological type of tumor, primary tumor site, tumor size, and previous treatment., From baseline to withdrawal of consent or death (whichever occurs first), up to 8 years|Exploratory outcome-Baseline and longitudinal on-treatment MR image characteristics associated with cCR or near cCR, MR image characteristics at baseline and their changes when tumor responded or progressed, From baseline to withdrawal of consent or death (whichever occurs first), up to 8 years