Biomarker Investigations for Clinical Trials

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

Biomarker for early drug development: We are extensively involved in biomarker studies to support clinical development of novel agents. For example, we were involved the biomarker studies for the first in phase Ia human study of a dual function immune-targeting agent M7824. Our data was the primary source of proof for the mechanism of action of this agent. Our data also provided the first set of information on the dose-response relationship, which is necessary for drug dose selection (Clin. Cancer Res. 24: 1287-1295, 2018). The drug is currently in advance stage of development by Merck KGaA and GSK. We have demonstrated ability to generate necessary data at early stage drug development. Biomarkers for patient management: We have deep experiences in protein biomarker assays with technologies from both Meso-Scale Diagnostics and Luminex Corp. We have further expertise in the clinical development and validation of novel protein biomarker assays that can used for treatment monitoring and for patient selection. We have recently developed and validated a new MPF tumor antigen test for mesothelioma (J Appl Lab Med. 3: 166-177, 2018). The assay has been evaluated and approved by the DCTD Biomarker Review Committee as an integrated biomarker for CTEP-sponsored multicenter trials across North America. We further showed in a retrospective study that this test is effective for patient monitoring, with antigen responses predictive of clinical outcome in the form of progress-free survival and overall-survival (JCO Precis Oncol. doi: 10.1200/PO.17.00282, 2018). We further observed the first association between an elevated tumor antigen level and a potential benefit for a targeted antibody therapy. We have committed to multiple NCI trials and three NCI-CTEP sponsored extramural studies to collect further evidence to support the development of a companion diagnostic with this tumor antigen. We also have exceptional experience in developing circulating blood-based HPV circulating tumor DNA (ctDNA) assay for the clinical development of T cell immunotherapies against HPV positive cancers (Clin Cancer Res. 23:6856-6862, 2017). We believe that the assay has a big potential as a non-invasive method for cancer patient selection and monitoring. We are currently in collaboration with Kite Pharma to develop it as a companion diagnostic for patient selection in the clinical development of T-Cell-Receptor immunotherapies for HPV+ cancers. Development of circulating tumor DNA technology to uncover cancer somatic mutation important for treatment response and resistance: To continue on our initial success with HPV ctDNA analysis, we are in advance stage of the development and validation of ctDNA based assays for cancer gene mutation detection and monitoring. Our technology enables the evaluation of approximately 300 cancer related genes from a tube of blood, as various time points of therapy. In the initial clinical studies with lung and cervical cancer patients, we showed that the assays are very effective in detecting and quantifying expected cancer gene mutations, and capable of providing critical novel information from these samples. We believe that this technology may have transformative effect for clinical trials at NCI.