Clinical trial NCT01603979: A Phase 1 Dose Escalation Study of AV-203, an ERBB3 Inhibitory Antibody, in Subjects With Advanced Solid Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: AV203
Solid Tumors
ERBB3
Monoclonal Antibody
HER3
Lead sponsor: AVEO Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-05-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of AEs, SAEs and Dose-limiting Toxicities (DLTs)
timeFrame: Ongoing throughout study. DLTs evaluated for first cycle of therapy. 1 cycle = 28 days
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of AV-203
timeFrame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
measure: Time to Cmax (Tmax) of AV-203
timeFrame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
measure: Area Under Plasma Concentration (AUC) of AV-203
timeFrame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
measure: Terminal phase half-life (t1/2) of AV-203
timeFrame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
measure: Clearance (Cl) of AV-203
timeFrame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
measure: Volume of Distribution (Vd) of AV-203
timeFrame: pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose
measure: Objective Response Rate (ORR)
timeFrame: Within 28 days of first dose and every 8 weeks while on study
measure: Disease Control Rate (DCR)
timeFrame: Within 28 days of first dose and every 8 weeks while on study
measure: Duration of Response (DOR)
timeFrame: Within 28 days of first dose and every 8 weeks while on study
measure: Time to Progression (TTP)
timeFrame: Within 28 days of first dose and every 8 weeks while on study
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: AVEO Clinical Site
state: Arizona
city: Atlanta
country: United States
facility: AVEO Clinical Site
state: Georgia
city: San Antonio
country: United States
facility: AVEO Clinical Site
state: Texas
Study officials:
References: