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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1 Open-label, Multiple Dose, Dose Escalation Study of Monoclonal Antibody AV-203 Administered in Subjects With Metastatic or Advanced Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Biological: AV-203


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-escalation AV-203 Monotherapy<br>dose-escalation of monotherapy AV-203 (an ERBB3 inhibitory antibody) by IV every two weeks | Biological: AV-203<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AV203, Solid Tumors, ERBB3, Monoclonal Antibody, HER3