CGI’s Response to the Genomics Gap in Renal Cancer Drug Development
Focus::Renal™ – The Most Comprehensive Molecular Profiling Tool for Kidney Cancer Clinical Testing & Clinical Trial Testing
The presentation, “Genomics of RCC” at the 3rd Annual Summit on Genitourinary Malignancies in NYC in October 2016 was by an internationally recognized leader in the area of genitourinary cancers Sumanta (Monty) Kumar Pal, MD. Dr. Pal presented clinical practice survey data remarking on the lack and need for molecular profiling of kidney (renal) cancer. Cancer Genetics, Inc. (CGI) has an answer to that lack and need!
Cancer Genetics, Inc. (Nasdaq: CGIX) has developed Focus::Renal™ – a unique, targeted, highly sensitive, and comprehensive next generation sequencing (NGS) panel to help facilitate an era of precision medicine for renal cancers.
Focus::Renal™ is the result of multiple independent validations and collaborations with prominent cancer centers and academic institutions, including Memorial Sloan Kettering Cancer Center (MSKCC), Cleveland Clinic, Huntsman Cancer Center at University of Utah, and University Hospital of Paris.
While many cancer incidence rates have declined over time, renal cancer incidence rates continue to rise. Renal cancer accounts for 5% of adult cancers in the United States with an estimated 62,700 new cases and 14,240 deaths in 2016 . The most common renal neoplasm is renal cell carcinoma (RCC). Clear cell RCC (ccRCC) accounts for ~75% of RCC, with other malignant subtypes papillary RCC (pRCC) and chromophobe RCC (chrRCC), and the benign neoplasm oncocytoma (OC) mostly comprising the remainder. ccRCC has a poorer prognosis than pRCC and chrRCC subtypes. About one fourth of the patients with ccRCC present with metastatic disease at diagnosis, while 20-40% of those with locally confined tumor tend to develop metastasis. ccRCC is a genomically well-characterized disease and genetic and epigenetic alterations ranging from single nucleotide polymorphisms (SNPs) to large chromosomal defects have been reported to be involved in disease outcome [2,3].
There are eight FDA-approved therapies including seven targeted therapies (including VEGF-TKIs sunitnib, sorafenib, pazopanib and axitinib; anti-VEGF monoclonal antibody bevacizumab; and mTOR inhibitors temsirolimus and everolimus) and one immunotherapy (anti-PD1 checkpoint inhibitor nivolumab) currently available to treat metastatic RCC – which makes therapy selection more challenging and yet more critical.
Currently, there is a growing body of evidence showing mutations, copy number changes (gain/loss), and certain polymorphisms correlate with patient outcome and therapy response, and are critical to enabling precision medicine. In addition, more than 200 clinical trials exist for renal cancer patients. At present, comprehensive genomic profiling of renal cancer patients has become an important need due to its potential impact on precision diagnostics and the development of tailor-made therapies, resulting in improved cancer care.
Focus::Renal™ is a comprehensive and accurate genomic profiling tool covering all major renal cancer markers and pathways. It is designed based on extensive scientific literature, The Cancer Genome Atlas (TCGA) genomic data, combined with in-house discoveries from our collaborations with leading research institutions as mentioned above, and has undergone multiple independent validations using samples from over 500 patients.
Focus::Renal™ is CLIA-validated, commercially-launched, and ready to take molecular profiling of renal cancer into the clinic. The test can be performed on a wide variety of patient specimen types, such as needle biopsies, fine-needle aspirates, and resected specimens using both formalin-fixed paraffin-embedded (FFPE) and fresh/fresh-frozen specimens, including the ones with minimal starting material, giving clinicians a choice on how to incorporate the test into their diagnostic workflow. We are currently validating this test in blood and plan on launching “Liquid Kidney” later this year as a liquid biopsy panel for cell-free DNA.
Focus::Renal™ is the only NGS panel to simultaneously detect mutations of 76 renal cancer-related genes, genome-wide copy number changes, and critical single nucleotide polymorphisms (SNPs), all in a single test, covering relevant drug pathways that enable precision diagnosis, prognosis, and therapy selection for renal cancer patients. It can also be utilized to distinguish among the dominant 3 malignant and 1 benign renal cancer subtypes, which is today largely driven by morphological and immunohistochemical review (which CGI can also provide). As we understand, it’s the only RCC-focused NGS panel commercially available today. We’ve seen rapid uptake by oncologists, as well as biopharma clients integrating this into the clinical trial biomarker strategies.
Among the 76 genes covered by the Focus::Renal™ panel are 9 major genes known to be frequently mutated in ccRCC, including VHL, PBRM1, SETD2, BAP1, ARID1A, TP53, MTOR, PIK3CA and TSC1. The panel also includes the coding regions of the following actionable drug targets – BRAF, RAF1, EGFR, ERBB2, PDGFRB, KIT and FLT3. Seven germline genetic polymorphisms/SNPs reported in the literature to be predictive of outcome in ccRCC are also included. Further, the panel also includes 50 less-frequently mutated genes according to TCGA cohort that map to regions of genomic imbalance /copy number alterations (CNAs) related to ccRCC progression. Lastly, the panel also contains target regions spaced at 3 megabases (Mb) apart across the genome to facilitate genome wide-copy number (>10 Mb size) estimation.
Focus::Renal™ will help facilitate the personalized care for renal cancer patients, as well as generate future insights for the development of more effective targeted therapies.
Stay tuned for more info about our progress to offer this panel as liquid biopsy from blood and urine. Several of our biopharma clients are already integrating our panel into their RCC trials.
Email me to set up a conference call to discuss our panel and how it can accelerate your RCC clinical programs!
Anna Israyelyan, MD, PhD
Clinical Affairs Manager
Tel: 323.224.3900 x175