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
2607 - Single cycle induction treatment with Cisplatin/Docetaxel plus Durvalumab/Tremelimumab in Stage III-IVB head and neck squamous cell cancer (CheckRad-CD8 trial)
Presenter: Markus Hecht
Session: Poster Display session 3
Resources:
Abstract
1388 - Radiotherapy plus cisplatin (CDDP) or cetuximab (C225) in human papilloma-virus (HPV)-associated oropharyngeal cancer (OPC)? A dillema finally resolved. An updated meta-analysis.
Presenter: Petar Suton
Session: Poster Display session 3
Resources:
Abstract
1478 - Treatment outcomes of head and neck cancer patients 70 years and older receiving different chemo-radiation combinations.
Presenter: Majd Issa
Session: Poster Display session 3
Resources:
Abstract
3985 - Brachytherapy and non-cancer mortality in patients with oral cavity and oropharynx SCCs
Presenter: Jovian Yu
Session: Poster Display session 3
Resources:
Abstract
4036 - Final results of a phase II study of induction chemotherapy (CT) with paclitaxel (PTX) and panitumumab (P) followed by radiotherapy (RT) and P in patients (pts) with locally advanced head and neck cancer (LAHNC) no candidates to platinum: study PANTERA
Presenter: Javier Martinez Trufero
Session: Poster Display session 3
Resources:
Abstract
4779 - Window of Opportunity for Durvalumab (MEDI4736) plus Metformin Trial in Squamous Cell Carcinoma of the Head and Neck (SCCHN): interim safety analysis
Presenter: Tony Richa
Session: Poster Display session 3
Resources:
Abstract
2757 - Severe Oral Mucositis (SOM) Mitigation by Genetically Modified Lactococcus Lactis Bacteria (LLB) Producing Human Trefoil Factor 1 (hTFF1; AG013) in Patients Being Treated With Concomitant Chemoradiation (CRT) for Oral and Oropharyngeal Cancers (OCOPC)
Presenter: Suraj Singh
Session: Poster Display session 3
Resources:
Abstract
5559 - Transcriptome signatures of treatment responses in a preoperative window of opportunity trial of nivolumab and tadalafil in resectable squamous cell carcinoma of the head and neck
Presenter: Sanket Shukla
Session: Poster Display session 3
Resources:
Abstract
3263 - Risk and Impact of Renal Impairment of Locally Advanced Head and Neck Squamous Cell Carcinoma Patients Who Received Chemoradiotherapy with Cisplatin
Presenter: Thana Patimarattananan
Session: Poster Display session 3
Resources:
Abstract
3128 - Systemic bevacizumab for the treatment of recurrent respiratory papillomatosis: A retrospective analysis from an academic tertiary care center
Presenter: Sumita Trivedi
Session: Poster Display session 3
Resources:
Abstract