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

NCT01603979 | Completed Phase 1

• 1 other identifier: AV-203-12-101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Solid Tumors

Keywords

AV203; Solid Tumors; ERBB3; Monoclonal Antibody; HER3

Outcome Measures

Primary Outcomes (1)

• Incidence of AEs, SAEs and Dose-limiting Toxicities (DLTs)

  Ongoing throughout study. DLTs evaluated for first cycle of therapy. 1 cycle = 28 days

Secondary Outcomes (10)

• 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

Study Arms (1)

Dose-escalation AV-203 Monotherapy

EXPERIMENTAL

dose-escalation of monotherapy AV-203 (an ERBB3 inhibitory antibody) by IV every two weeks

Biological: AV-203

Interventions

AV-203 BIOLOGICAL

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.

Dose-escalation AV-203 Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (3)

AVEO Clinical Site

Scottsdale, Arizona, 85258, United States

Location

AVEO Clinical Site

Atlanta, Georgia, 30322, United States

Location

AVEO Clinical Site

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Interventions

AV-203

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2012
• First Posted: May 23, 2012
• Study Start: May 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 8, 2015

Record last verified: 2015-04

Locations

US (3)