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PDF file - 81K, Supplementary Table 2 Primers and probe sets utilized in this study were designed by the Primer Express 1.5 software and synthesized by Sigma-Aldrich. These primers and probes were utilized for quantitative PCR in ancillary biologic studies, and the data

PDF file - 106K, Patients were then assigned into one of three Ad5.SSTR/TK.RGD dose cohorts ranging from 1 x 109 vp/d to 1 x 1012 vp/d (6 x 107 pfu/d to 6 x 1010 pfu/d). This dose administration strategy has been validated in our preclinical studies; assigned Ad5.SSTR/TK

Purpose: Ad5.SSTR/TK.RGD is an infectivity-enhanced adenovirus expressing a therapeutic thymidine kinase suicide gene and a somatostatin receptor (SSTR) that allows for noninvasive gene transfer imaging. The purpose of this study was to identify the maximum tolerated dose (MTD), toxicities, clinical efficacy, and biologic effects of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer.Experimental Design: Eligible patients were treated intraperitoneally for 3 days with 1 × 109 to 1 × 1012 vp/dose of Ad5.SSTR/TK.RGD followed by intravenous ganciclovir for 14 days. Toxicity and clinical efficacy were assessed using Common Toxicity Criteria (CTC) Adverse Events grading and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Imaging using In-111 pentetreotide was obtained before and after treatment. Tissue samples were obtained to evaluate for gene transfer, generation of wild-type virus, viral shedding, and antibody response.Results: Twelve patients were treated in three cohorts. The most common vector-related clinical toxicities were grade I/II constitutional or pain symptoms, experienced most often in patients treated at the highest dose. MTD was not identified. Five patients showed stable disease; all others experienced progressive disease. One patient with stable disease experienced complete resolution of disease and normalization of CA125 on further follow-up. Imaging detected increased In-111 pentetreotide retention in patients treated at the highest dose. Ancillary studies showed presence of Ad5.SSTR/TK.RGD virus and HSV1-tk expression in ascites samples collected at various time points in most patients treated within the higher dose cohorts.Conclusions: This study shows the safety, potential efficacy, and possible gene transfer imaging capacity of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Further development of this novel gene therapeutic appears to be warranted. Clin Cancer Res; 18(12); 3440–51. ©2012 AACR.

PDF file - 51K, Patients were then assigned into one of three Ad5.SSTR/TK.RGD dose cohorts ranging from 1 x 109 vp/d to 1 x 1012 vp/d (6 x 107 pfu/d to 6 x 1010 pfu/d). This dose administration strategy has been validated in our preclinical studies; assigned Ad5.SSTR/TK

Objective: We investigated the potential role of molecular profiling through next generation sequencing (NGS) to identify actionable gene mutations in tumors of recurrent ovarian cancer patients that could impact clinical care decisions. Methods: Under IRB approval, patients diagnosed with recurrent ovarian cancer from 9/2015 to 3/2016 underwent NGS of archival tumor specimens utilizing a 65 gene panel performed by Washington University's Genomics and Pathology Services (GPS) or a 315 gene FoundationOne (FO) panel performed by Foundation Medicine. Select patients also underwent NGS of circulating cell free DNA (cfDNA) from blood specimens utilizing a 50 gene panel performed at Circulogene Theranostics. Genomic alterations found from cfDNA in the blood at the time of recurrence were compared to alterations found in archival tumor tissue. The effect of therapies selected on the basis of NGS testing was assessed. Results: Specimens from 95 recurrent ovarian cancer patients have been collected; 54 had the GPS gene panel and 35 had the FO gene panel. Six patient samples were unable to be sequenced due to inadequate tumor DNA. 44 patients were sequenced with the 50 gene cfDNA panel at Circulogene; four patient samples did not have detectable cfDNA and were unable to be sequenced. 30 patients have had both NGS on tumor and cfDNA. A range of 0 to15 mutations were detected by the GPS or FO NGS panel with an average of 3.7 mutations per tumor sample. A range of 0 to 6 mutations were detected on cfDNA panel with an average of 1.7 mutations per patient. The most frequent mutation detected by GPS, FO, and Circulogene was TP53. Of the 30 patients with both tumor and cfDNA sequenced, only 7 patients were found to have a TP53 genomic alteration in both the tumor and cfDNA. In all other patients where both cfDNA and tumor DNA had NGS performed, there was no concordance between the tumor and the cfDNA genomic alterations. Of the 95 patients, three patients were started on targeted therapy based on their results (Olaparib for a somatic BRCA mutation [without a germline mutation], Pazopanib for a FGFR mutation, Everolimus for a CTNNB1 mutation). Targeted therapy is being pursued in 6 additional patients: Trametinib for a patient with a KRAS mutation, Nivolumab for a patient with high microsatellite instability, Everolimus for 3 patients with PIK3CA mutations or a PTEN mutation, and Pertuzumab for a patient with a ERBB3 mutation. A somatic BRCA mutation was found in nine patients, seven of which also have a germline BRCA mutation. Conclusion: Ovarian cancer has a diverse genetic landscape and molecular profiling via NGS offers the opportunity to identify genetic alterations that can be utilized to direct therapy. Approximately 15% of patients with recurrent ovarian cancer have a mutation that can be targeted with a commercially available drug. We have been successful in providing patients with a mutation the NGS-directed therapy. Challenges still exist with the large variation in NGS technology and reporting and further research is needed to better identify actionable oncogenic drivers. Citation Format: Angelina I. Londono, Naveed Farrukh, Mary Kat Smith, Cindy M. Tawfik, Ronald D. Alvarez, Warner K. Huh, Kerri S. Bevis, Charles A. Leath, III, Straughn Michael, Jr., Eddy Shih Hsin Yang, Shuko Harada, Kenneth H. Kim, Rebecca C. Arend. Analysis of Clinical Cancer Gene Panels by Next Generation Sequencing in Tumor and Circulating Cell-Free DNA Samples in Recurrent Ovarian Cancer Patients [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr B29.