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

Sponsor

AVEO Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01603979

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Biological: AV-203	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Dec 1, 2014

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	AVEO Clinical Site	Scottsdale	Arizona	United States	85258
2	AVEO Clinical Site	Atlanta	Georgia	United States	30322
3	AVEO Clinical Site	San Antonio	Texas	United States	78229