TR1801-ADC in Patients With Tumors That Express c-Met

Study Overview
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Brief Summary
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First-in-human, Phase 1 study to assess safety, tolerability, and pharmacokinetics of TR1801-ADC in patients with select solid tumors that express c-Met.

Detailed Description
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First-in-human, Phase 1, multiple dose-dose escalation study designed to determine safety, tolerability, maximum tolerated dose, and recommended phase 2 dose of TR1801-ADC in patients with select solid tumors that express c-Met. This study will also assess pharmacokinetics (PK), anti-tumor activity, and correlation between clinical outcomes (safety, anti-tumor activity, and PK) and c-Met expression.

Official Title
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A Phase 1, Open Label, First-in-human Study of TR1801-ADC, an Antibody Drug Conjugate (ADC), in Patients With Select Solid Tumors Expressing c-Met

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: TR1801-ADC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Compliance with all study procedures and visits to the clinical research site Locally advanced or metastatic disease that is not amenable to definitive therapy Histologically confirmed diagnosis of a solid tumor which expresses c-Met Must have progressed or have been intolerant to all available therapies known to confer clinical benefit appropriate for the patient's tumor type Measurable baseline disease as defined by RECIST Version 1.1 ECOG Performance Status 0-1 Body weight within 40 and 150 kg Clinical laboratory values with the limits as defined by the protocol Not pregnant or breast feeding Males and women of child-bearing potential must agree to use an effective method of contraception Exclusion Criteria: Any disease or condition that may be considered to pose an increased risk from study treatment or the ability of the patient to participate and comply with study procedures Treatment with anti-cancer therapy (including cytotoxic chemotherapy, major surgery, radiation, biologic and investigational agents) within 21 days before first dose of study treatment Brain metastases that has not stabilized for at least 28 days after therapy and who have discontinued steroids for <2 weeks Unresolved adverse events >= Grade 2 from prior anticancer therapies Acute myocardial infarction, cerebral ischemic infarct, or other arterial thrombosis within 6 months of screening for this study. Uncontrolled hypertension, unstable angina, or NYHA Class III/IV heart failure History of capillary leak syndrome Corticosteroid intolerance History of anasarca Untreated or uncontrolled bacterial, viral or fungal infection HIV infection or active infection with hepatitis B or C Significant liver disease History of alcoholism or current alcoholism Signs of significant portal hypertension Significant kidney disease within 2 years Active or unstable gallstone disease Prior treatment with a c-Met targeted agent Prior hypersensitivity reaction to treatment with another monoclonal antibody QTcF >=470 ms Patients may not start any new herbal or dietary supplement within 4 weeks before initiation of study treatment nor while receiving study treatment Administration of a live, attenuated vaccine within 28 days before the first dose of study treatment

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
Interventional Model Description: Open label, multiple dose, dose-escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TR1801-ADC<br>Humanized anti-c-Met monoclonal antibody conjugated to a cleavable pyrrolobenzodiazepine toxin | Biological: TR1801-ADC<br>* Humanized anti-c-Met monoclonal antibody conjugated to a cleavable pyrrolobenzodiazepine toxin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize safety of TR1801-ADC in patients with advanced solid tumor malignancies which express c-Met | Number of participants with treatment-related adverse events | 4 years | 
| Establish maximum tolerated dose | Number of participants with protocol-defined dose-limiting toxicity | 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate pharmacokinetics of TR1801-ADC | Analyze blood plasma concentrations | 4 years | 
| Immunogenicity | Assess anti-drug antibodies of TR1801-ADC | 4 years | 
| Evaluate clinical activity of TR1801-ADC | Assess objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST V1.1) | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibody-drug conjugate, c-Met, solid tumors, Phase 1