Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
antibody-drug conjugate, c-Met, solid tumors, Phase 1
Brief summary
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
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.
Interventions
BIOLOGICALTR1801-ADC
Humanized anti-c-Met monoclonal antibody conjugated to a cleavable pyrrolobenzodiazepine toxin
Sponsors
Open Innovation Partners, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label, multiple dose, dose-escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterize safety of TR1801-ADC in patients with advanced solid tumor malignancies which express c-Met | 4 years | Number of participants with treatment-related adverse events |
| Establish maximum tolerated dose | 3.5 years | Number of participants with protocol-defined dose-limiting toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate pharmacokinetics of TR1801-ADC | 4 years | Analyze blood plasma concentrations |
| Immunogenicity | 4 years | Assess anti-drug antibodies of TR1801-ADC |
| Evaluate clinical activity of TR1801-ADC | 5 years | Assess objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST V1.1) |
Countries
United States
Outcome results
None listed