Data from A Phase I Clinical Trial of Ad5.SSTR/TK.RGD, a Novel Infectivity-Enhanced Bicistronic Adenovirus, in Patients with Recurrent Gynecologic Cancer

• DOI: 10.1158/1078-0432.c.6520214.v1
• Publication Date: 2023-04-01T07:00:34Z
• Authors: Kenneth H. Kim; Igor Dmitriev; Janis P. O'Malley; Minghui Wang; Souheil Saddekni; Zhiying You; Meredith A. Preuss; Raymond D. Harris; Rosemarie Aurigemma; Gene P. Siegal; Kurt R. Zinn; David T. Curiel; Ronald D. Alvarez

<div>Abstract<p><b>Purpose:</b> Ad5.SSTR/TK.RGD is an infectivity-enhanced adenovirus expressing a therapeutic thymidine kinase suicide gene and somatostatin receptor (SSTR) that allows for noninvasive transfer imaging. The purpose of this study was to identify the maximum tolerated dose (MTD), toxicities, clinical efficacy, biologic effects in patients with recurrent gynecologic cancer.</p><p><b>Experimental Design:</b> Eligible were treated intraperitoneally 3 days 1 × 10<sup>9</sup> 10<sup>12</sup> vp/dose followed by intravenous ganciclovir 14 days. Toxicity efficacy assessed using Common Criteria (CTC) Adverse Events grading Response Evaluation Solid Tumors (RECIST) criteria. Imaging In-111 pentetreotide obtained before after treatment. Tissue samples evaluate transfer, generation wild-type virus, viral shedding, antibody response.</p><p><b>Results:</b> Twelve three cohorts. most common vector-related toxicities grade I/II constitutional or pain symptoms, experienced often at highest dose. MTD not identified. Five showed stable disease; all others progressive disease. One patient disease complete resolution normalization CA125 on further follow-up. detected increased retention Ancillary studies presence virus <i>HSV1-tk</i> expression ascites collected various time points within higher cohorts.</p><p><b>Conclusions:</b> This shows safety, potential possible imaging capacity cancer. Further development novel appears be warranted. <i>Clin Cancer Res; 18(12); 3440–51. ©2012 AACR</i>.</p></div>