Treatment of ARB202 Advanced Gastrointestinal Cancer Patients

Study Overview
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Brief Summary
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This study aims to find out: The tolerability of ARB202 in adults with advanced solid gastrointestinal tumors who failed the standard treatment. People can participate if their tumor has the CDH17 marker. To find out how study drug is broken down in the body To know the effects of the study drug on the tumor.

Official Title
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A Phase 1, First-in-human Study of ARB202, Bispecific Antibody to CDH17 and CD3 in Advanced Gastrointestinal Malignancies

Conditions
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Gastrointestinal Cancer, Cholangiocarcinoma, Liver Cancer, Colorectal Adenocarcinoma, Pancreatic Cancer, Gastric Cancer

Intervention / Treatment
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* Drug: ARB202


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed colorectal, pancreatic, gastric adenocarcinoma, primary liver cancer or metastatic liver disease, or cholangiocarcinoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Malignancies should possess with ≥10% expression of CDH17 confirmed by immunohistochemistry except for CRC patients. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. Life expectancy > 3 months. Measurable disease as defined by RECIST 1.1 criteria Blood coagulation parameters: PT INR ≤ 1.5X ULN PTT INR ≤1.2X ULN Patients must have adequate venous peripheral access for apheresis. Satisfactory organ and bone marrow function as defined by: absolute neutrophil count > 1,000/μL platelets >100,000/μL hemoglobin ≥9 g/dL serum ALT and AST ≤ 3X ULN or AST and ALT ≤5X ULN, if liver function abnormalities are thought to be from underlying malignancy total serum bilirubin ≤ 2X ULN Creatinine <1.5X ULN Stable amylase for 2 weeks Exclusion Criteria: Prior gene therapy or therapy with any murine monoclonal antibodies or any murine containing product. Concurrent treatment with any anticancer agent including chemotherapy, hormonal therapy or radiation therapy. Must be 5 X half-life or 6 weeks (whichever is shorter) post dosing of previous cancer therapies. History of allergy or hypersensitivity to murine proteins or study product excipients Females who are pregnant, trying to become pregnant, or breastfeeding. Diagnosis of HIV or chronic active viral hepatitis (HBV, HCV, HIV). Active infection requiring systemic treatment. Active brain, leptomeningeal, or paraspinal metastases, except for asymptomatic metastases and are stable on a steroid dose of ≤ 10mg/day of prednisone or its equivalent for at least 14 days prior to the start of study interventions. Impaired cardiac function (AHA NY Heart Association Grade II-IV) or clinically significant cardiac disease. Lack of recovery of prior CTCAE Grade 3 or above adverse events due to earlier therapies. Chronic use of corticosteroids in excess of >10mg daily of prednisone or equivalent within 4 weeks prior to alopecia. Concomitant use of complementary or alternative medication or therapy such as Chinese herbal medicine. History of Crohn's disease, inflammatory bowel disease, or ulcerative colitis within the past 5 years Abnormal bowel function which would make assessment of bowel permeability difficult to access Major trauma or major surgery within 4 weeks prior to first dose of study drug

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1a: Dose Escalation<br> | Drug: ARB202<br>* ARB202 Atezolizumab<br>|
| Experimental: Phase 1b: Low dose ARB202<br> | Drug: ARB202<br>* ARB202 Atezolizumab<br>|
| Experimental: Phase 1b: High dose ARB202<br> | Drug: ARB202<br>* ARB202 Atezolizumab<br>|
| Experimental: Phase 1b: Low dose ARB202 + Immune Checkpoint Inhibitor<br> | Drug: ARB202<br>* ARB202 Atezolizumab<br>|
| Experimental: Phase 1b: High dose ARB202 + Immune Checkpoint Inhibitor<br> | Drug: ARB202<br>* ARB202 Atezolizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events |  | 8 weeks post initial dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of ARB202 in plasma after single and multiple doses of ARB202 in patients |  | 16 weeks | 
| Biochemical and physiological effects of ARB202 on the amount of circulating ARB202 level in patients |  | 16 weeks | 
| Biochemical and physiological effects of ARB202 on the amount of soluble CDH17 level in patients |  | 16 weeks | 
| Biochemical and physiological effects of ARB202 on the amount IL-2 level in patients |  | 16 weeks | 
| Effect of ARB202 on tumour as determined by changes in RECIST evaluation from baseline |  | 6 weeks |