Biomarker Investigations for Clinical Trials

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

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. 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). 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. 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. 2. Identification of new biomarkers. A) In working with Dr. Steven Pavletic, we developed new cytokine tests for the investigation of graft vs host disease (Curtis LM Blood. 137:896-907. 2021; Goklemez S Bone Marrow Transplant. doi: 10.1038/s41409-021-01419-2. 2021). B) Preclinical investigation of tumor biomarker in animal models. The work with Dr. Christine Alewine is to better design the clinical study and to improve the value of the biomarker investigation. Some of the research was published (Zhang X, Transl Oncol, doi: 10.1016/j.tranon.2022.101440. 2022), with others to follow. 3. Assay development and validation. A) In response to COVID-19 pandemic, we developed a high-performance serology test for COVID-19. In addition, we also developed a test to evaluate an assay to evaluate the ACE2 receptor binding of various SARS-cov-2 variants. We generated extensive clinical data with donors who had COVID-19 or vaccination in collaboration with Dr. Kamille West of NIH Clinical Center (Yu Y, Sci Rep, 12:2628. doi: 10.1038/s41598-022-06629-2. 2022). 4. New technology development. A) We focus on the development of a circulating tumor DNA based technology for determining cancer gene mutations associated with treatment responses, and for the identification of mutations associated with resistance. We successfully developed new NGS-based assays to examine somatic mutations involved in the process of antigen presentation and T cell response using cell free DNA. The work is to support trials by Dr. Christian Hinrichs, who was succeeded by Dr. Scott Norberg. B) We are working on cell free DNA test for the investigation of potential neoplasia in pregnant women presented with abnormal NIPT test results in a trial led by Dr. Christina Annunziata and Dr. Diana Bianchi of NICHD.