Kimberley S Samkoe, Hira Shahzad Sardar, Jason R Gunn, Jonathan Thomas Elliott, Sally Mansur, Joachim Feldwisch, Brian W Pogue, Konstantinos Linos, Keith D Paulsen, Eric R Henderson
{"title":"First-in-human Study of ABY-029, a Novel Fluorescent Peptide that Targets Epidermal Growth Factor Receptor, Applied to Soft-Tissue Sarcomas.","authors":"Kimberley S Samkoe, Hira Shahzad Sardar, Jason R Gunn, Jonathan Thomas Elliott, Sally Mansur, Joachim Feldwisch, Brian W Pogue, Konstantinos Linos, Keith D Paulsen, Eric R Henderson","doi":"10.1158/1535-7163.MCT-24-0378","DOIUrl":null,"url":null,"abstract":"<p><p>ABY-029, an anti-epidermal growth factor receptor (EGFR) Affibody® molecule conjugated to IRDye 800CW, recently underwent first-in-human testing in soft-tissue sarcoma (STS). FDA Exploratory Investigational New Drug status was obtained for the Phase 0 clinical trial in which study objectives were to determine whether biological variance ratio (BVR) of 10 was achievable, fluorescence intensity correlated with EGFR expression, and doses were well tolerated. Patients (N=12) with STS were recruited based on positive EGFR immunohistochemical staining of diagnostic biopsies. ABY-029 was administered at micro- (30 nanomole, n=3), medium (90 nanomole, n=3), or high dose (171 nanomole, n=6), 1-3 hours prior to surgery. Following tumor resection, ex vivo tissue was imaged to determine mean fluorescence intensity (MFI), BVR, and other contrast measures. EGFR expression was correlated with immunohistochemistry. For micro-, medium, and high doses, mean BVR (SD) in cross-sectional slices were 4 (4), 10 (6), and 7 (8), respectively, for the whole tumor region and 6 (5), 13 (11), and 8 (6), respectively, for pathology-confirmed regions-of-interest. Strong linear correlations were found between all ABY-029 contrast metrics and total EGFR (r≥0.86, p<0.029) in cross-sectional tissue slices, and MFI and EGFR percent area (r=0.63, p<0.0001) in excised region-of-interest tissue sections. No ABY-029 related adverse events were observed. When administered above the microdose, ABY-029 demonstrated high correlation to EGFR expression and contrast values that were encouraging for translation to clinical practice. Contrast was similar to those observed with antibody agents, but with substantially reduced imaging-to-resection time, and no drug-related adverse events.</p>","PeriodicalId":18791,"journal":{"name":"Molecular Cancer Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Cancer Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1535-7163.MCT-24-0378","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
First-in-human Study of ABY-029, a Novel Fluorescent Peptide that Targets Epidermal Growth Factor Receptor, Applied to Soft-Tissue Sarcomas.
ABY-029, an anti-epidermal growth factor receptor (EGFR) Affibody® molecule conjugated to IRDye 800CW, recently underwent first-in-human testing in soft-tissue sarcoma (STS). FDA Exploratory Investigational New Drug status was obtained for the Phase 0 clinical trial in which study objectives were to determine whether biological variance ratio (BVR) of 10 was achievable, fluorescence intensity correlated with EGFR expression, and doses were well tolerated. Patients (N=12) with STS were recruited based on positive EGFR immunohistochemical staining of diagnostic biopsies. ABY-029 was administered at micro- (30 nanomole, n=3), medium (90 nanomole, n=3), or high dose (171 nanomole, n=6), 1-3 hours prior to surgery. Following tumor resection, ex vivo tissue was imaged to determine mean fluorescence intensity (MFI), BVR, and other contrast measures. EGFR expression was correlated with immunohistochemistry. For micro-, medium, and high doses, mean BVR (SD) in cross-sectional slices were 4 (4), 10 (6), and 7 (8), respectively, for the whole tumor region and 6 (5), 13 (11), and 8 (6), respectively, for pathology-confirmed regions-of-interest. Strong linear correlations were found between all ABY-029 contrast metrics and total EGFR (r≥0.86, p<0.029) in cross-sectional tissue slices, and MFI and EGFR percent area (r=0.63, p<0.0001) in excised region-of-interest tissue sections. No ABY-029 related adverse events were observed. When administered above the microdose, ABY-029 demonstrated high correlation to EGFR expression and contrast values that were encouraging for translation to clinical practice. Contrast was similar to those observed with antibody agents, but with substantially reduced imaging-to-resection time, and no drug-related adverse events.
期刊介绍:
Molecular Cancer Therapeutics will focus on basic research that has implications for cancer therapeutics in the following areas: Experimental Cancer Therapeutics, Identification of Molecular Targets, Targets for Chemoprevention, New Models, Cancer Chemistry and Drug Discovery, Molecular and Cellular Pharmacology, Molecular Classification of Tumors, and Bioinformatics and Computational Molecular Biology. The journal provides a publication forum for these emerging disciplines that is focused specifically on cancer research. Papers are stringently reviewed and only those that report results of novel, timely, and significant research and meet high standards of scientific merit will be accepted for publication.