A Study of the Safety and Pharmacology of MetMAb (PRO143966), a Monovalent Antagonist Antibody to the Receptor C-Met, Administered Intravenously in Patients With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This is a Phase I, open label, dose-escalation study of MetMAb administered by intravenous (IV) infusion in patients with advanced solid malignancies that are refractory to or for which there is no standard of care. The study consists of a dose-escalation stage, an expansion stage testing MetMAb at the recommended Phase II dose (RP2D), and a dose-escalation stage testing the combination of MetMAb, at two different doses with bevacizumab at a recommended dose.

Official Title
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A Phase I, Open Label, Dose Escalation Study of the Safety and Pharmacology of MetMAb (PRO143966), a Monovalent Antagonist Antibody to the Receptor C-Met, Administered Intravenously in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Solid Cancers

Intervention / Treatment
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* Drug: bevacizumab
* Drug: MetMAb
* Drug: MetMAb


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic documentation of incurable, locally advanced, or metastatic solid malignancy that has failed to respond to at least one prior regimen or for which there is no standard therapy Disease that is measurable or evaluable by Response Evaluation Criteria In Solid Tumors (RECIST) Life expectancy ≥12 weeks Exclusion Criteria: Less than 4 weeks since the last anti-tumor therapy Patients receiving erythropoietin products Active infection requiring antibiotics Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy Clinically important history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis Known human immunodeficiency virus infection Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases

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: Stage I<br> | Drug: MetMAb<br>* Repeating escalating intravenous dose<br>|
| Experimental: Stage II<br> | Drug: MetMAb<br>* Repeating intravenous dose<br>|
| Experimental: Stage III<br> | Drug: bevacizumab<br>* Repeating intravenous dose<br>Drug: MetMAb<br>* Repeating escalating intravenous dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of MetMAb alone or in combination with bevacizumab will be assessed (frequency and nature of dose-limiting toxicities; nature, severity, and relatedness of adverse events; changes in vital signs and clinical laboratory parameters) |  | Length of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response, defined as a complete or partial response confirmed ≥4 weeks after initial documentation |  | Length of study | 
| Duration of objective response |  | Length of study | 
| Progression-free survival |  | Length of study |