Phase I Study of U3P1287/01, Including Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1 clinical study to investigate the safety, pharmacokinetics, and pharmacodynamics of U3-1287 (AMG 888), a fully human monoclonal antibody targeting the HER3 receptor, in patients with advanced solid tumors. Eligible patients will have disease that is refractory or resistant to standard treatments or for which no standard therapy exists. The study will be conducted in two parts; a dose escalation (Part 1) and a dose expansion (Part 2). The hypothesis for this study is that U3-1287 (AMG888) will be safe and well tolerated in patients with advanced solid tumors and will show initial evidence of anti-tumor activity.

Official Title
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A Phase I, Open-label, Dose-Finding Study to Assess the Safety and Tolerability of U3-1287 (AMG 888), a Human Monoclonal Antibody Targeting HER3 in Patients With Advanced Solid Tumors.

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: U3-1287 (AMG888)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Pathologically or cytologically documented advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available, or the patient refuses standard therapy. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Men or women at least 18 years of age Adequate hematologic, cardiac, renal, hepatic, metabolic, and coagulation function Key Exclusion Criteria: Presence of untreated or symptomatic brain metastasis. Presence of ascites or pleural effusion requiring chronic medical intervention. Uncontrolled hypertension Concurrent or previous (within 1 week of study day 1) anticoagulation therapy, except low-dose warfarin (≤ 2 mg/day) or low dose,low molecular weight heparin for prophylaxis against central venous catheter thrombosis. Recent major surgical procedure or not yet recovered from major surgery Recent participation in clinical drug trials. Participation in other investigational procedures. Unresolved toxicities from prior anti-cancer therapy Patient who is pregnant (e.g. positive human choriogonadotropin [HCG] test) or nursing.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: U3-1287 (AMG888)<br>* IV Infusion Dose Escalation (Part 1) - 5 Dose Cohorts Dose Expansion (Part 2) - 30 patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of U3-1287 (AMG888) in patients with advanced solid tumors |  | Lenth of study | 
| To evaluate maximum tolerated dose (MTD) of U3-1287(AMG888) when administered intravenously to patients with advanced solid tumors |  | Lenth of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters |  | Length of study | 
| Pharmacodynamic Parameters |  | Length of study | 
| Human anti-human antibody profile for U3-1287(AMG888) |  | Length of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Epidermal Growth Factor Receptor 3, HER3, Heregulin, erb B3, Solid Tumors, Phase I Clinical Study