Solid Tumors
Conditions
Keywords
AV203, Solid Tumors, ERBB3, Monoclonal Antibody, HER3
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.
Interventions
BIOLOGICALAV-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.
Sponsors
AVEO Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Maximum Plasma Concentration (Cmax) 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 |
| Volume of Distribution (Vd) of AV-203 | pre-dose, 5 min, 15 min, 7 hr, 24 hr, 168 hr post-dose |
Countries
United States
Outcome results
None listed