TST001 in Patients With CLDN18.2 Positive Previously Treated Advanced Biliary Tract Cancer

Study Overview
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Brief Summary
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TST001 is a recombinant humanized anti-Claudin 18.2 (CLDN18.2) IgG1 monoclonal antibody. This is an open-label, single-arm phase II study to evaluate the efficacy and safety of TST001 for patients with CLDN18.2 positive previously treated unresectable advanced or metastatic Biliary Tract Cancer.

Detailed Description
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TST001 is a recombinant humanized anti-Claudin 18.2 (CLDN18.2) IgG1 monoclonal antibody. Claudin18.2 (CLDN18.2) protein is one of the family of tetraspanning proteins expressed at epithelial tight junctions and primarily expressed only in normal gastric tissues . CLDN18.2 protein is a pancancer target expressed in primary lesions and metastases of variouscancer types, including gastric cancer, biliary tract cancer and others. Current available information indicates that CLDN18.2 is a promising therapeutic target for the treatment of solid tumors. This is an open-label, single-arm phase II study to evaluate the efficacy and safety of TST001 for patients with CLDN18.2 positive previously treated unresectable advanced or metastatic Biliary Tract Cancer. Eligible patients will be treated with TST001 until disease progression or other discontinuation criteria met. If there is ≥ one objective response among the first 15 enrolled patients, then the trial continues to enroll a total of 40 patients; if not, then the trial discontinues.

Official Title
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An Open-label, Single-arm Phase II Study to Evaluate the Efficacy and Safety of TST001 for Patients With CLDN18.2 Positive Previously Treated Unresectable Advanced or Metastatic Biliary Tract Cancer

Conditions
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Biliary Tract Neoplasms

Intervention / Treatment
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* Drug: TST001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, unresectable advanced or metastatic biliary tract cancer. Patients failed at least one prior line of systemic medications; if patients had disease progression during or within 6 months after the completion of adjuvant therapy or neoadjuvant therapy, the adjuvant therapy or neoadjuvant therapy could be regarded as one line of therapy. CLDN18.2 expression positive confirmed through tumor tissue. Patients with at least one measurable disease according to RECISTv1.1. ECOG PS of 0 or 1. Patients have predicted life expectancy ≥ 12 weeks. Paitients with adequate cardica, liver, renal function, etc. Exclusion Criteria: • History of another concurrent primary malignancy. Untreated or symptomatic CNS metastases. Prior treatment targeting CLDN18.2. Major surgical procedure, prior locoregional therapy such as radioembolization within 28 days prior to the first dose of study drug. Prior serious hypersensitivity to monoclonal antibody or any component of the investigational drug. Patients had any of the following within 6 months prior to first dose of study treatment: cerebrovascular accident, transient ischemic attack, myocardial infarction or unstable angina pectoris, heart failure NYHA III or IV degree, or uncontolled uarrhythmia requiring intervention. Patients who are pregnant or lactating.

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: TST001<br>Drug: TST001 IV infusion every 3 weeks until disease progression or other discontinuation criteria. | Drug: TST001<br>* TST001 IV infusion every 3 weeks until disease progression or other discontinuation criteria.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | ORR according to RECIST 1.1 using investigator assessment | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS accorridng RECSIST1.1 using investigator assessment | 18 months | 
| Overall survival | Time from enrollment to death of any cause | 18 months | 
| DoR | DoR accroding to RECSIST1.1 using investigator assessment | 18 months | 
| DCR | Patients who were assessed as partial response, complete response or stable disease | 18 months | 
| Safety & tolerability | Adverse events will be graded according to NCI-CTC AE v5.0 | 18 months |