Abstract 2963
Background
Metastatic castration-resistant prostate cancer (mCRPC) patients with DNA repair gene defects (DRD) have a shorter life expectancy than patients without DRD and may benefit from treatment with PARP inhibitors. Niraparib is a highly selective PARP inhibitor, with activity against PARP-1/2 DNA-repair polymerases. Detection of DRD in cell free DNA (cfDNA) isolated from blood is minimally invasive and of special benefit to mCRPC patients, including patients without accessible lesions. The assay would also have the advantage of a shorter turnaround time (TAT) than genotyping of tissue. However, using cfDNA to identify biallelic disruption of DNA-repair genes is technically challenging.
Methods
Resolution-HRD identifies patients with biallelic pathogenic alterations of the ATM, BRCA1, BRCA2, BRIP1, CHEK2, FANCA, HDAC2, or PALB2 genes, by targeted NGS sequencing of cfDNA. Analytical performance of Resolution-HRD was validated using cfDNA from mCRPC patient plasma, cfDNA from healthy donor plasma, and contrived samples with a wide spectrum of technically challenging genetic aberrations.
Results
The LOD95 at a cfDNA input level of 40 ng ranged from 0.2 to 1.37 for SNVs and indels, and 6-12 for CNL. APA for intra-run and inter-run studies at the 1X LOD was 95% and 95% respectively. No false-positives were detected in any samples from healthy donors (N = 60). Resolution-HRD has been validated to give consistent results across the 10-75 ng input range. Resolution-HRD is used to identify patients for enrollment in the GALAHAD Phase II Efficacy and Safety Study (64091742PCR2001) of Niraparib in Men with mCRPC and DNA-Repair Anomalies. As of April 2019, over 2000 patients are tested successfully (0.88% failure rate) with a median TAT of 8.6 days (range 5-12 days).
Conclusions
The analytical performance of the Resolution-HRD assay offers highly sensitive, specific and robust test results, and meets analytical requirements for clinical applications. This test is currently being evaluated in several clinical trials for prospective identification of mCRPC patients with DRD for treatment with niraparib.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Resolution Bioscience.
Funding
Janssen Research and Development.
Disclosure
I. Pekker: Shareholder / Stockholder / Stock options, Full / Part-time employment: resolution bioscience. L. Lim: Leadership role, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment, Officer / Board of Directors: Resolution Bioscience. J.S. Simon: Leadership role, Shareholder / Stockholder / Stock options: Janssen. M. Gormley: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. Z. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: Resolution Bioscience. J. Pollak: Shareholder / Stockholder / Stock options, Full / Part-time employment: Resolution Bioscience. K. Potts: Shareholder / Stockholder / Stock options, Full / Part-time employment: Resolution Bioscience. S. Watford: Shareholder / Stockholder / Stock options, Full / Part-time employment: Resolution Bioscience. J. Posey: Shareholder / Stockholder / Stock options, Full / Part-time employment: Resolution Bioscience. P. Chan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Resolution Bioscience. K. Urtishak: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen. K. Garg: Shareholder / Stockholder / Stock options, Full / Part-time employment: Resolution Bioscience. A. Hosseini: Shareholder / Stockholder / Stock options, Full / Part-time employment: Resolution Bioscience. M. Li: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Resolution Bioscience.
Resources from the same session
5760 - Landscape of PD-L1 expression status in Chinese solid tumor patients.
Presenter: Yi Zhong
Session: Poster Display session 3
Resources:
Abstract
3733 - Anti-cancer and immunomodulatory effects of cobimetinib in triple negative breast cancer
Presenter: Chun-Yu Liu
Session: Poster Display session 3
Resources:
Abstract
4426 - Differential expression of immunoregulatory molecules and highly-associated cancer genes may provide novel insights into strategic trial design for therapeutics
Presenter: Jacob Adashek
Session: Poster Display session 3
Resources:
Abstract
2752 - Insights into the Tumor Immune Microenvironment using Tissue Phenomics to Drive Cancer Immunotherapy
Presenter: Martin Groher
Session: Poster Display session 3
Resources:
Abstract
5713 - Immune competent somatic mosaic model of colorectal cancer
Presenter: Stefania Napolitano
Session: Poster Display session 3
Resources:
Abstract
1898 - Genomic correlates of response to anti-PDL1 Atezolizumab in non-small-cell lung cancer OAK and POPLAR trials
Presenter: Hari Singhal
Session: Poster Display session 3
Resources:
Abstract
3246 - Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
3311 - High level of activity of Nivolumab anti-PD-1 immunotherapy and favorable outcome in metastatic/refractory MSI-H non-colorectal cancer: Results of the MSI cohort from the French AcSé program
Presenter: Christophe Tournigand
Session: Poster Display session 3
Resources:
Abstract
2314 - TP53 and ATM Co-mutation Predicts Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
Presenter: Yu Chen
Session: Poster Display session 3
Resources:
Abstract
4692 - Immune cell biomarkers on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA NSCLC patients
Presenter: Raquel Laza-Briviesca
Session: Poster Display session 3
Resources:
Abstract