A Study of AMG 820 in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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First in human, open-label, sequential dose escalation and expansion study of AMG 820 in subjects with advanced solid tumors.

Official Title
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A Phase 1, First-In-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacokinetics of AMG 820 in Adult Subjects With Advanced Solid Tumors

Conditions
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Advanced Malignancy, Advanced Solid Tumors, Cancer, Oncology, Oncology Patients, Tumors

Intervention / Treatment
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* Drug: AMG 820


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥ 18 years old Subjects must have a pathologically documented, definitively diagnosed, advanced solid tumor Measurable disease per RECIST 1.1 guidelines Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 Part 2 - Dose Expansion only: Subjects must have tumor tissue that is accessible for core needle biopsy by using minimally invasive procedures and must consent to undergo biopsies of the tumor Able to fast 4 to 6 hours for FDG-PET/CT scan, except subjects with prostate or bladder cancers Competent to sign and date an Institutional Review Board approved informed consent form Adequate hematologic, renal and hepatic function as determined by laboratory blood and urine tests Exclusion Criteria: Men and woman of reproductive potential, unwilling to practice a highly effective method of birth control for the duration of the study and an additional 4 months after receiving the last dose of study drug. Women who are lactating/breastfeeding or planning to become pregnant during the duration of the study Primary central nervous system (CNS) tumors or CNS metastases History of presence of hematological malignancies History of arterial or venous thrombosis within 6 months of study enrollment History of bleeding diathesis Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication, or uncontrolled hypertension Hypertension not adequately controlled with medication (diastolic > 90mmHG; systolic > 140 mmHG) Left ventricular ejection fraction (LVEF) ≤ 50% Active infection requiring (IV) antibiotics within 2 weeks of study enrollment Known positive test for human immunodeficiency virus (HIV) Known chronic hepatitis B or hepatitis C infection Positive test for hepatitis B surface antigen or hepatitis C antibody Known history of tuberculosis (TB), exposure to active TB-infected individuals, or positive TB skin test (tuberculin or purified protein derivative (PPD) test) upon study entry (subjects previously vaccinated for TB are not excluded unless there is evidence of active TB) Anti-tumor therapy within 4 weeks of study day 1 including chemotherapy, antibody therapy, retinoid therapy, or other investigational agent Concurrent or prior anticoagulation therapy within 28 days of study day 1 Major surgery within 28 days of study day 1 Any co-morbid medical disorder that may increase the risk of toxicity, in the opinion of the investigator or sponsor

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: Dose Expansion<br>The dose expansion will consist of up to 20 subjects and the dose level of AMG 820 will be dependent upon emerging safety and PK data from the dose escalation part of the study. | Drug: AMG 820<br>* AMG 820 is a fully human IgG2 c-fms antagonistic antibody and will be given every two weeks until progression or unacceptable toxicity develops.<br>|
| Experimental: Dose Escalation<br>The dose escalation part of the study is aimed at evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of AMG 820. | Drug: AMG 820<br>* AMG 820 is a fully human IgG2 c-fms antagonistic antibody and will be given every two weeks until progression or unacceptable toxicity develops.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under Curve (AUC) Time Frame: predose, 0.5, 1, 2, 4, 8, 24 hours post-dose |  | 3 years | 
| Dose of AMG 820 where clinically significant or ≥ Grade 3 changes in safety laboratory tests, physical examinations, ECGs, or vitals signs in all subjects enrolled is greater than 33%. |  | 3 years | 
| Change in tumor associated macrophages (TAMS) as assessed by tumor biopsy at 9 weeks. |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumors, Phase 1, Clinical Trial