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

Purpose

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.

Condition	Intervention	Phase
Solid Tumors	Biological: AV-203	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1 Open-label, Multiple Dose, Dose Escalation Study of Monoclonal Antibody AV-203 Administered in Subjects With Metastatic or Advanced Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by AVEO Pharmaceuticals, Inc.:

Primary Outcome Measures:

Incidence of AEs, SAEs and Dose-limiting Toxicities (DLTs) [ Time Frame: Ongoing throughout study. DLTs evaluated for first cycle of therapy. 1 cycle = 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Maximum Plasma Concentration (Cmax) of AV-203 [ Time Frame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose ] [ Designated as safety issue: No ]
Time to Cmax (Tmax) of AV-203 [ Time Frame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose ] [ Designated as safety issue: No ]
Area Under Plasma Concentration (AUC) of AV-203 [ Time Frame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose ] [ Designated as safety issue: No ]
Terminal phase half-life (t1/2) of AV-203 [ Time Frame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose ] [ Designated as safety issue: No ]
Clearance (Cl) of AV-203 [ Time Frame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose ] [ Designated as safety issue: No ]
Volume of Distribution (Vd) of AV-203 [ Time Frame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose ] [ Designated as safety issue: No ]
Objective Response Rate (ORR) [ Time Frame: Within 28 days of first dose and every 8 weeks while on study ] [ Designated as safety issue: No ]
Disease Control Rate (DCR) [ Time Frame: Within 28 days of first dose and every 8 weeks while on study ] [ Designated as safety issue: No ]
Duration of Response (DOR) [ Time Frame: Within 28 days of first dose and every 8 weeks while on study ] [ Designated as safety issue: No ]
Time to Progression (TTP) [ Time Frame: Within 28 days of first dose and every 8 weeks while on study ] [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	May 2012
Estimated Study Completion Date:	October 2014
Estimated Primary Completion Date:	May 2014 (Final data collection date for primary outcome measure)

Intervention Details:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01603979

Contacts

Contact: Philip Komarnitsky, MD

617-299-5654

pkomarnitsky@aveooncology.com

Locations

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

Sponsors and Collaborators

AVEO Pharmaceuticals, Inc.

More Information

No publications provided

Responsible Party:	AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01603979 History of Changes
Other Study ID Numbers:	AV-203-12-101
Study First Received:	May 21, 2012
Last Updated:	January 22, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by AVEO Pharmaceuticals, Inc.:

AV203
Solid Tumors
ERBB3
Monoclonal Antibody
HER3

Additional relevant MeSH terms:

Neoplasms
Antibodies
Immunoglobulins
Antibodies, Monoclonal

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013