Immune Checkpoint Inhibitors for Organ Preservation in Non-metastatic dMMR/MSI-H Gastric or Colon Cancers
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorPeking University
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Subjects are able to comprehend the informed consent form, and voluntarily sign the informed consent form.
Subjects are ≥18 years old on the day of signing the informed consent form, with no gender restrictions.
Histologically confirmed gastric cancer or colon cancer, without distant metastasis based on CR or MR.
ECOG performance status of 0-2.
Disqualifiers
Distant metastasis;
Previous treatment including CTLA4 blockade;
Subjects with interstitial lung disease or a history of non-infectious pneumonia requiring oral or intravenous corticosteroid treatment.
Subjects with active autoimmune diseases requiring systemic treatment before the start of the study or those considered at risk of recurrence or planned treatment for autoimmune diseases as judged by the investigator. Except for these conditions: a) skin diseases that do not require systemic treatment (e.g., vitiligo, alopecia, psoriasis, or eczema); b) hypothyroidism caused by autoimmune thyroiditis, requiring stable doses of hormone replacement therapy; c) type 1 diabetes requiring stable doses of insulin replacement therapy; d) childhood asthma fully resolved with no need for intervention in adulthood; e) the investigator judges that the disease will not relapse without external triggering factors.
Trial design
Design model
Single group
Treatments tested in this trial
PD1/PDL1 antibody monotherapy, up to 24 weeks
Drugnon-specific, according to Drug Instructions
Intensive immunotherapy plus anti-VEGF treatment, up to 24 weeks
Combination productSintilimab 200mg, ivgtt, q21d; IBI310 1mg/kg, ivgtt, q42d; Lenvatinib 8mg (starting from 4mg), po, qd
Radical surgery
Procedure/SurgeryRadical surgery will be recommended per local treatment standards.
Treatment groups
34 Participants
are divided into 2 treatment groupsGroup A: dMMR/MSI-H gastric cancerExperimental treatment 3 interventions
Group B: dMMR/MSI-H colon cancerExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
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 LenvatinibSecondary outcomes
1
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
Time frame
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 weeks2
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
Time frame
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 Lenvatinib3
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
Time frame
Baseline up to withdrawal of consent, progressive disease, unacceptable toxicity, or surgery (whichever occurs first), up to 8 years4
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
Time frame
Baseline up to withdrawal of consent, progressive disease, unacceptable toxicity, or surgery (whichever occurs first), up to 8 yearsOther outcomes
1
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.
Time frame
From baseline to withdrawal of consent or death (whichever occurs first), up to 8 years2
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.
Time frame
From baseline to withdrawal of consent or death (whichever occurs first), up to 8 years3
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.
Time frame
From baseline to withdrawal of consent or death (whichever occurs first), up to 8 years4
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
Time frame
From baseline to withdrawal of consent or death (whichever occurs first), up to 8 yearsSponsors and contacts
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Source ClinicalTrials.gov