Biomarker Investigations for Clinical Trials

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Related to the specific 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 marker investigation of Dr. Andrea Apolo by investigating the drug effects on angiogenesis and inflammation. The work was recently published (Lancet Oncol. 21: 1099-1109, 2020). B) We provided biomarker analyses for an antiangiogenic therapy study by Dr. Jung-min Lee (Gynecol Oncol. 159: 88-94, 2020). C) We conducted the biomarkers studies in a trial by Dr. Vladimir Valera on an EpCAM antibody, vicinium, in combination with immunotherapy. In the study, we develop both PD and PK assays for the drug, as well as conduct immune cytokine profiling for the trial. Our results provided the first informative PK data on vicinium and the trial is on-going. D) 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 a number of HPV-targeted therapy trials by Dr. Christian Hinrichs, who is succeeded by Dr. Scott Norberg. We also successfully evaluated our assay in MRD monitoring of plasma somatic mutations in a checkpoint/vaccine study on prostate cancer. 2. Identification of new biomarkers. A) We worked with Dr. Ira Pastan and Raffit Hassan to uncover biomarkers for treatment monitoring and response prediction. The early results were published (JCO Precis Oncol. doi: 10.1200/PO.17.00282, 2018), and we continuously support a number of NCI trials by Dr. Hassan and Dr. Alewine on mesothelin-targeted agents. B). In working with Dr. Steven Pavletic, we developed new cytokine tests for the investigation of graft vs host disease (Am J Hematol. 95: 387-394, 2020 and Blood 137: 896-907, 2020). 3. Assay development and validation. A) We developed a new tumor antigen test and carried extensive analytic and clinical validation (J Appl Med Lab. 3:166-177, 2018), leading to the approval of the test by NCI Biomarker Committee for applications of multiple NCI-sponsored multicenter trials. We currently three multicenter trials with this test to assess its ability for treatment monitoring and patient selection. This test is also used to support various mesothelin-targeted antibody or T cell therapies by Dr. Raffit Hassan and Christine Alewine. B) We developed a cell free DNA for patient selection and treatment monitoring of HPV positive cancer patients on adoptive T cell therapies (Clin Cancer Res. 23:6856-6862, 2017). We have conducted a joint assay validation with Kite Pharma and have the assay transfer to their operation for treatment monitoring and patient selection. C) 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. A manuscript was submitted for publication. 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.