A Phase 1 Dose Escalation Study of AMG 780 in Adult Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a first in human, open-label, sequential dose escalation and expansion study of AMG 780 in up to 62 subjects with advanced solid tumors. The dose escalation part of the study is aimed at evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of AMG 780. The dose expansion will consist of up to 20 subjects and the dose level of AMG 780 will be dependent upon emerging safety and PK data from the dose escalation part of the study.

Official Title
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A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 780 in Adult Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: AMG 780


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥ 18 years old Must have a pathologically documented, and definitely diagnosed, advanced solid tumor that is refractory to standard treatment, or for which no curative therapy is available, or for subjects who refuse standard therapy Measurable disease by RECIST criteria Must be able to undergo MRI evaluation Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Competent to sign and date an Institutional Review Board approved informed consent form Exclusion Criteria: Presence of untreated or symptomatic primary central nervous system tumors or metastases Presence of leukemia or myelodysplastic syndrome Subjects with head and neck cancer Previous hematopoietic stem cell transplant (allogeneic) Unresolved hematological toxicities > grade 1 with the exception of grade 2 lymphopenia and non-hematological toxicities > grade 1, excluding alopecia and grade 2 neuropathy, from prior anti-cancer therapy Myocardial infarction within 1 year before study day 1, or unstable or uncontrolled disease/condition related to or affecting cardiac function History of stroke, arterial or venous thrombosis, or pulmonary embolism within 1 year before study Active peripheral vascular disease History of bleeding diathesis History of pulmonary hemorrhage or gross hemoptysis within 6 months before study Known history of adrenal hemorrhage Known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C Major surgery within 1 month before study Prior treatment with any agent targeting the angiopoietin-Tie2 signaling pathway Concurrent antitumor treatment, except Lupron for subjects with prostate cancer and selective estrogen receptor modulators (SERMS) for subjects with breast cancer, within 4 weeks (6 weeks for nitrosoureas or mitomycin) before study day 1 Known sensitivity to mammalian-derived products, bacterially-produced proteins, or any of the products to be administered during dosing Investigational agent within 30 days before study Pregnant (eg, positive urine test) or breastfeeding Subjects of childbearing potential, or subject who has a partner of childbearing potential, and is not using highly effective contraceptive precautions

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: A<br>Dose Escalation | Drug: AMG 780<br>* AMG 780 will be administered by IV infusion every 2 weeks<br>|
| Experimental: B<br>Dose Expansion | Drug: AMG 780<br>* AMG 780 will be administered by IV infusion every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of AMG 780 in subjects with advanced solid malignancies (including adverse event rate, incidence of dose-limiting toxicities, and determination of maximum tolerated dose) |  | 2.5 years | 
| To evaluate the pharmacokinetic (PK) parameters of AMG 780 including, but not limited to Cmax, AUC, and accumulation ratio |  | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate tumor response using RECIST criteria (measured by CT/MRI) |  | 2.5 years | 
| To evaluate changes in tumor volume (measured by volumetric CT/MRI) |  | 2.5 years | 
| To evaluate changes in tumor vascularity and to estimate the relationship between dose/pharmacokinetics and vascular response (measured by DCE-MRI) |  | 2.5 years | 
| To evaluate the incidence of anti-AMG 780 antibody formation |  | 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First-In-Human, Dose Escalation, Dose Expansion, Advance Solid Tumors, Anti-Angiopoietin, Advance Malignancy, Cancer, Oncology, Oncology Patients, Phase 1, Clinical Trial, Tumors, Solid Tumors, Angiogenesis Inhibitors