KN035 for dMMR/MSI-H Advanced Solid Tumors

Study Overview
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Brief Summary
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In this study, patients with previously-treated locally-advanced or metastatic mismatched repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal carcinoma (CRC) and other solid tumors will be treated with KN035 monotherapy. For colorectal cancer participants, who are required to have been previously treated with standard therapies or refuse standard therapy, other solid tumor participants, who are required to have been previously treated with at least one line of systemic standard of care therapy.

Detailed Description
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Later-line therapies after failure of standard treatments for advanced colorectal and non-colorectal cancer patients are limited. Mismatch repair (MMR) deficiency or microsatellite instability-high (MSI-H) played a role of positive predictive factor, which had been documented after the pembrolizumab and nivolumab trial were reported, for PD-1 blockade monotherapy in patients with advanced colorectal and non-colorectal cancers. In this study, patients with previously-treated locally-advanced or metastatic mismatched repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal carcinoma (CRC) and other solid tumors will be treated with KN035 monotherapy. For colorectal cancer participants, who are required to have been previously treated with standard therapies or refuse standard of care therapy. For other solid tumor participants, who are required to have been previously treated with at least one line of systemic standard of care therapy.

Official Title
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Study of KN035 as Monotherapy in Patients With Advanced Mismatched Repair Deficient (dMMR) or Microsatellite Instability-High (MSI-H) Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Biological: KN035


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed locally advanced or metastatic colorectal carcinoma or other malignant solid tumors. Confirmed MMR deficient or MSI-H status. At least one measureable lesion. Eastern Cooperative Oncology Group performance status of 0 or 1 . Life expectancy of greater than 12 weeks. Adequate hematologic and organ function. Exclusion Criteria: Currently participated in a study of an investigational agent and received trial treatment, or used an investigational device within 4 weeks of the first dose of medication in this study. Patients who have had specific anti-tumor treatment within 2 weeks prior to the first dose of study. Patients who have not recovered to CTCAE Grade 1 or better from related side effects of any prior antineoplastic therapy. Has received prior therapy with an immune check point agonist/inhibitor. Patients who have undergone major surgery within 4 weeks of dosing of investigational agent. Has a known additional malignancy that is progressing or requires active treatment within the past 5 years. Known active central nervous system metastases and/or carcinomatous meningitis. Active autoimmune disease that has required systemic treatment. Patients who have known history of infection with HIV. Patients with evidence of interstitial lung disease. Patients who have known history of any major cardiac abnormalities. Patient who is not willing to apply highly effective contraception during the study. Patients who have other concurrent severe and/or uncontrolled medical conditions that would, in the investigator's judgment, contraindicate patient participation in the clinical 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects with MSI-H/dMMR<br>patients receive KN035 300 mg Subcutaneously biweekly | Biological: KN035<br>* subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | per Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by central imaging vendor | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | per Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by investigator | Up to approximately 2 years | 
| Disease Control Rate (DCR) | per RECIST 1.1 assessed by central imaging vendor and investigator | Up to approximately 2 years | 
| Duration of Response (DOR) | per RECIST 1.1 assessed by central imaging vendor and investigator | Up to approximately 2 years | 
| Progression-Free Survival (PFS) | per RECIST 1.1 assessed by central imaging vedor and investigator | Up to approximately 2 years | 
| Overall Survival (OS) | Calculated by the Kaplan-Meier method. | Up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MSI-H, dMMR, Colorectal cancer, Non-Colorectal Cancers