A Phase 1 Dose Escalation Study of AV-203, an ERBB3 Inhibitory Antibody, in Subjects With Advanced Solid Tumors

A Phase 1 Open-label, Multiple Dose, Dose Escalation Study of Monoclonal Antibody AV-203 Administered in Subjects With Metastatic or Advanced Solid Tumors

This is a Phase 1, multi-center, open-label, multiple dose, dose escalation study to evaluate the safety, tolerability, dose limiting toxicities (DLTs), maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D), pharmacokinetic (PK), pharmacodynamics, and preliminary anti-tumor activity of AV-203, an ERBB3 inhibitory antibody, administered once every 2 weeks via intravenous (IV) infusion in subjects with metastatic or advanced solid tumors. Once the RP2D is determined, patients with tumor types of interest will be evaluated in an expansion cohort at the RP2D for safety and anti-tumor activity.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Biological: AV-203

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • AVEO Clinical Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • AVEO Clinical Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • AVEO Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 years of age
• Histologically and/or cytologically confirmed primary diagnosis
• Metastatic or advanced solid tumor, that has recurred or progressed following standard therapies, or for which no standard therapy exists
• Must have available tumor tissue or be willing to undergo biopsy prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
• Blood Chemistry and Hematology results within defined limits

Exclusion Criteria:

• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent
• Current central nervous system (CNS) or leptomeningeal metastases, or history of CNS or leptomeningeal metastases.
• Significant conduction disturbance, history of a severe arrhythmia, or history of a familial arrhythmia
• Significant cardiovascular disease
• Significant thromboembolic or vascular disorders within prior 3 months
• Any other medical condition or psychiatric condition that, in the opinion of the Investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results
• Known history of positive results for hepatitis C, hepatitis B, or human immunodeficiency virus.
• For female subjects, pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-escalation AV-203 Monotherapy; dose-escalation of monotherapy AV-203 (an ERBB3 inhibitory antibody) by IV every two weeks	Biological: AV-203; The antibody AV-203 is a humanized immunoglobulin G1/kappa (IgG1/κ) monoclonal antibody that targets the receptor tyrosine kinase (RTK) ERBB3 and inhibits ERBB3 activities. AV-203 will be administered as a 60 to 75-minute IV infusion once every 2 weeks until disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of AEs, SAEs and Dose-limiting Toxicities (DLTs)	Ongoing throughout study. DLTs evaluated for first cycle of therapy. 1 cycle = 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax) of AV-203	pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
Time to Cmax (Tmax) of AV-203	pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
Area Under Plasma Concentration (AUC) of AV-203	pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
Terminal phase half-life (t1/2) of AV-203	pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
Clearance (Cl) of AV-203	pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
Volume of Distribution (Vd) of AV-203	pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
Objective Response Rate (ORR)	Within 28 days of first dose and every 8 weeks while on study
Disease Control Rate (DCR)	Within 28 days of first dose and every 8 weeks while on study
Duration of Response (DOR)	Within 28 days of first dose and every 8 weeks while on study
Time to Progression (TTP)	Within 28 days of first dose and every 8 weeks while on study

Collaborators and Investigators

• Sponsor: AVEO Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: May 21, 2012
• First Submitted That Met QC Criteria: May 22, 2012
• First Posted (Estimate): May 23, 2012

Study Record Updates

• Last Update Posted (Estimate): April 8, 2015
• Last Update Submitted That Met QC Criteria: April 6, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Monoclonal Antibody; Solid Tumors; AV203; ERBB3; HER3
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AV-203-12-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No