Biomarker Investigations for Clinical Trials

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The collaborative studies with Drs. Gulley and Lassoued on a clinical prostate cancer trial (NCT02933255) evaluating a combination therapy of the cancer vaccine PROSTVAC with the programmed cell death protein-1 inhibitor nivolumab were summarized and published during the last year with Dr. Kang from the GB Omics team as a co-author. In collaboration with Dr. Diana Bianchi of NICHD, we conducted a pivotal study involving somatic mutation analysis from cell free DNA in pregnant women with abnormal Noninvasive Prenatal Testing (NIPT) results. This study involved pioneering work to uncover tumor-specific somatic mutations informing on cancer origins, common pathogenic processes, and treatment drug options. Using a state-of-the-art pipeline, we identified somatic and germline variants, as well as copy number alterations, from cfDNA and matched PBMC samples. Major results were confirmed using an updated variant calling pipeline developed by the GB Omics Bioinformatics team with UMI-based error correction and manual review. The results of the study present significant novel knowledge in the field which could impact the clinical management of patients 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. The manuscript comprising the first 65 patient samples is currently in revision with Dr. Kang as the lead author. Kang Z, Turriff AE, Cao L, Bianchi DW. Evaluation of somatic mutations in cell-free DNA as noninvasive biomarkers of cancer in asymptomatic pregnant women (in revision) Dr. Kang is currently working on an additional 140 samples of this precious patient cohort to further validate the important findings in larger patient numbers. As indicated in the "Goals and Objectives", a major current focus for the GB Omics Facility is the correlative science support for clinical trial NCT06865664, a study investigating the effect of FGFR4 chimeric antigen receptor (CAR) T cells in children and young adults with recurrent or refractory rhabdomyosarcoma, Currently, wet lab assays, SOPs and bioinformatics pipelines are being established to support this trial. Specifically, we are using our fragmentomics expertise to optimize cfDNA assays for monitoring treatment response. Establishing a novel methylation assay (Biomodal) is an important goal. We are also developing a Human Anti-Chimeric Antibody (HACA) assay to track antibodies directed against the chimeric therapeutic antibody, potentially reducing its effectiveness. In addition, we will provide low pass WG, exome and RNA-Seq analysis from FFPE tumor material and will be flexible to establish any additional assays needed to support this trial and any future clinical trials within the Genetics Branch.