Biomarker Investigations for Clinical Trials

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Related to the specific biomarker goals above, we conducted various studies to support biomarker driven early-stage drug development: 1. Application of new or novel biomarkers in early-stage trials of highly unique therapeutic agents. A) We supported correlative marker investigations of Dr. Raffit Hassan on his mesothelin-targeted novel therapies, including traditional antibody drug conjugate therapies, and T cell therapies, using the assay that we have previously developed (JCO Precis Oncol. doi: 10.1200/PO.17.00282, 2018). Significant responses were seen in many patients, where our tumor antigen tests were performed in near real time to provide investigators with timely information on responses and on progression. According to the new focus of our facility, the project was completed from our side and assay capabilities were transferred to Dr. Hassan's lab. B) We provided continues biomarker support of clinical trials by Dr. Andrea Apolo and some of the work was published (Girardi DM, Clin Cancer Res, doi: 10.1158/1078-0432. 2022). This project has been finalized and is terminated. C) We developed a cell free DNA detection for cervical cancer and use it for treatment monitoring, minimum residue disease (MRD) detection, cancer genotyping for patient selection. We support HPV-targeted therapy trials by Dr. Scott Norberg. Some of the recent work was focused on using NGS with cell free DNA for resistance mechanisms against T cell therapies. Also this project was completed and terminated. D) Somatic mutation analysis with cell free DNA in pregnant women with abnormal chromosome test results. In working with Christina Annunziata and Dr. Diana Bianchi of NICHD, we performed some pioneer work to uncover tumor specific somatic mutation informing on cancer origins, on common pathogenic processes, and on treatment drug options. Interim results presented some significant novel knowledge in the field which could impact the patient clinical management and inform on the feasibility of using chromosome aneuploidy for cancer screening. We focus on the development of a circulating tumor DNA based technology for predicting the development of cancer in pregnant women and for determining cancer gene mutations associated with cancer. We are currently working on a cell free DNA test for the investigation of potential neoplasia in pregnant women who presented with abnormal NIPT test results in a trial led by Dr. Diana Bianchi of NICHD.