A Microdose Evaluation Study of ABY-029 in Primary Sarcoma

Study Overview
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Brief Summary
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The primary study objective is to determine if microdoses of ABY-029 (up to 6X) lead to detectable signals (defined as signal-to-noise ratio, SNR ≥10, with the Odyssey NIR scanner in sampled tissues with an EGFR pathology score ≥ 1 based on histological staining and compare SNR to tissues with an EGFR pathology score < 1). The secondary study objective is to assess if the spatial patterns of EGFR expression correlate with the tumor targeting of ABY-029 detection by NIR scanner relative to histopathology diagnosis, and other indicators (e.g. proliferation, infiltration, etc.) as the gold standard, and to measure the molecular uptake and concentration of ABY-029 in resected specimens.

Detailed Description
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The investigators plan to enroll a minimum of 6 and a maximum of 12 adult patients with a diagnosis of primary soft-tissue sarcoma in this open label, single center, clinical trial of ABY-029. The study will enroll patients with an EGFR pathology score ≥ 1. Initial diagnostic biopsy specimens will be analyzed for EGFR positivity by immunohistochemistry following routine diagnostic processing by Pathologist. Patients will be administered a single intravenous dose of ABY-029 1-3 hours before surgery. Following tumor excision, the tumor will be transported to the Pathologist and will be inked and sectioned. Following sectioning the tumor will be imaged using near-infrared imaging systems. Quantitative measurements of fluorophore concentration will be measured for tumors with EGFR pathology score ≥ 1 and compared to those with EGFR pathology score < 1. Quantitative mapping of fluorophore concentration will be correlated with local EGFR concentration and blood vessel density. Upon specimen analysis, fluorophore measurements will be taken from normal, marginal tissues (e.g. skeletal muscle, adipose) in addition to the tumor. Average EGFR concentration and blood vessel density will be determined for each tumor through histological analysis of sections by routine sarcoma protocol and analysis guided by regional variations in ABY-029 concentration based upon near-infrared scan results. The protocol is not a safety study since no physiological effects are expected at microdose levels of ABY-029. No diagnostic or therapeutic intent is proposed, and administration of the study drug is not intended to alter the extent of planned tumor resection during the surgical procedure.

Official Title
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A Phase 0 Open Label, Single-center Clinical Trial of ABY-029, an Anti-EGFR Fluorescence Imaging Agent Via Single Intravenous Injection to Subjects With Primary Sarcoma.

Conditions
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Primary Soft-tissue Sarcoma

Intervention / Treatment
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* Drug: ABY-029


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preoperative histological diagnosis of primary sarcoma. Tumor judged to be suitable for open surgical resection based on preoperative imaging studies. Valid informed consent by subject. Age ≥ 18 years old. Exclusion Criteria: Pregnant women or women who are breast feeding. Patients on any experimental anti-EGFR targeted therapies, either investigational or FDA approved.

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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABY-029<br>ABY-029 will be administered prior to surgery and tissue will be examined ex vivo to determine binding with EGFR positive tumor tissue. | Drug: ABY-029<br>* A minimum of 6 and a maximum of 12 adult patients with a diagnosis of primary soft-tissue sarcoma will be enrolled. Initial diagnostic biopsy specimens will be analyzed for EGFR positivity (an EGFR pathology score ≥ 1) by immunohistochemistry following routine diagnostic processing by Pathologist. Patients will be administered a single intravenous dose of ABY-029 1-3 hours before surgery.<br>* Other names: IRDye® 800CW Maleimide labeled Affibody peptide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Signal detection | Following tumor excision, the tumor will be inked and sectioned and imaged using a near-infrared scanner and fiber-probe based system. Quantitative measurements of fluorophore concentration will be measured for tumors with EGFR pathology score ≥ 1 and compared to those with EGFR pathology score < 1. | Day of surgery, up to 1 week after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of spatial patterns of EGFR expression | Quantitative mapping of fluorophore concentration will be correlated with local EGFR concentration and blood vessel density. | within 1 week of surgery | 
| molecular uptake and ABY-029 concentration | Fluorophore measurements will be taken from normal, marginal tissues (e.g. skeletal muscle, adipose) in addition to the tumor. Average EGFR concentration and blood vessel density will be determined for each tumor through histological analysis of sections by routine sarcoma protocol and analysis guided by regional variations in ABY-029 concentration based upon near-infrared scan results. | within 1 week of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABY-029, Affibody, molecular fluorescence-guided surgery, Epidermal Growth Factor Receptor (EGFR)