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Caris Life Sciences Launches Significant Enhancements to Industry-leading Cancer Tumor Profiling Service

Caris Life Sciences®, a leading biosciences company focused on fulfilling the promise of personalized medicine, recently launched significant enhancements to its Molecular Intelligence™ tumor profiling service. These enhancements include significant updates to MI Portal™, the company’s online physician resource, a streamlined molecular profiling panel structure and the addition of two biomarkers.

Nektar Presents Target-Specific Biomarkers Being Assessed in Ongoing Phase 3 BEACON Study of Etirinotecan Pegol for the Treatment of Metastatic Breast Cancer at the 2013 American Society of Clinical Oncology Annual Meeting

Nektar Therapeutics (NASDAQ:NKTR) recently announced that it presented a series of target-specific biomarkers that are being evaluated in the development of etirinotecan pegol for the treatment of breast cancer. Etirinotecan pegol is a unique, next generation, targeted topoisomerase I inhibitor currently in Phase 3 clinical development as a potential treatment for patients with locally recurrent or metastatic breast cancer. The BEACON (BrEAst Cancer Outcomes with NKTR-102) Phase 3 Study is a randomized, open-label, international study that is evaluating single agent etirinotecan pegol in patients who have previously received an anthracycline, a taxane and capecitabine (ATC) versus a comparator arm consisting of an active single agent treatment of physician’s choice (TPC).

“One of our objectives in treating metastatic breast cancer is to prospectively identify patients that will respond to specific treatments so they can achieve the optimal individualized care,” said Hope Rugo, M.D., Director of Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Comprehensive Cancer Center and Member of the BEACON Study investigator steering committee. “The goal of evaluating these important biomarkers in patients enrolled into the BEACON study is to help us understand which breast cancer patients might have the best clinical outcomes from treatment with etirinotecan pegol.”

A series of assays for target-specific pharmacodynamic biomarkers for etirinotecan pegol, including the molecular target topoisomerase I, have been established and are being measured in the Phase 3 BEACON study. The biomarkers were identified from Circulating Tumor Cell (CTC) samples which were collected prior to patient treatment. Additional CTC patient samples are being collected at regular intervals during treatment and at the end of treatment. Preliminary results from the initial pre-dose samples found CTCs in over 90% of patient samples, with a median of 200 CTCs per 7.5 mL blood draw. Patient participation in the CTC sub-set of the BEACON study is projected to be over 75%. Measurements of each biomarker expression over time will be analyzed in order to identify potential predictive biomarkers for clinical response to etirinotecan pegol.

“We are pleased to have identified several baseline pharmacodynamic biomarkers, which are target-specific such as topoisomerase 1, and which can be reliably measured over the patient’s treatment period,” said Robert Medve, M.D., Chief Medical Officer of Nektar Therapeutics. “The measurement of these biomarkers in the BEACON study will help us understand and shape the future treatment of patients with etirinotecan pegol. Enrollment in the BEACON study is well ahead of schedule and we expect to complete the target enrollment of 840 patients in the third quarter of 2013.”

Circulating Tumor Cells are cancer cells shed from either the primary tumor or its metastases that circulate in the peripheral blood. CTCs are emerging tumor biomarkers, collected through a minimally invasive blood draw, providing a “liquid” biopsy sample and allowing for post-treatment monitoring of the patient. CTCs provide well-defined targets for the understanding of tumor biology and tumor cell dissemination, which offers a unique approach to identify novel therapeutic targets and understand resistance to established therapies.

Source: Nektar Therapeutics

bioTheranostics’ CancerTYPE ID® More Accurate than Immunohistochemistry in Diagnosing Metastatic Tumors

bioTheranostics’ CancerTYPE® ID molecular cancer classifier demonstrated superior accuracy compared with immunohistochemistry (IHC) in identifying the primary site in difficult-to-diagnose metastatic tumors. The comparative effectiveness study, which was published recently in The Journal of Molecular Diagnostics, is the first comprehensive investigation to directly compare the diagnostic accuracy of the two tumor classification techniques.

“Timely, accurate, and definitive diagnosis is the critical first step, particularly as patient outcomes continue to improve with appropriate site-specific and molecular-targeted therapies. We are delighted to see CancerTYPE ID’s superiority in performance compared with the standard-of-care IHC.”
In this blinded study conducted in collaboration with the City of Hope National Medical Center, high-grade, primarily metastatic tumors considered diagnostically challenging were selected by lead investigators Lawrence M. Weiss, M.D., and Peiguo Chu, M.D. Performance of CancerTYPE ID for diagnosis of tumor type was directly compared with IHC analysis in 122 cases. Results were scored using reference diagnoses established by detailed clinical correlation.

In these difficult-to-diagnose cancers, CancerTYPE ID, a 92-gene RT-PCR assay, demonstrated a statistically significant improvement of 10 percent in overall accuracy compared with IHC (p=0.019). Performance differences favoring CancerTYPE ID were more than 20 percent when greater than nine IHC stains were used, likely due to the poorly differentiated nature of the cancers. These findings highlight CancerTYPE ID’s immediate clinical utility when an initial IHC panel does not lead to a definitive diagnosis, and when tumor specimen is limited and expanded IHC testing is likely to exhaust tissue that may be needed for predictive biomarker testing.

More than 400,000 patients present with metastatic cancer each year in the United States. Metastatic cancers of unknown or uncertain primary origin pose significant challenges for physicians to select appropriate therapies. “Precision Medicine involves individualized patient care based on tumor biology,” said Richard Ding, CEO of bioTheranostics. “Timely, accurate, and definitive diagnosis is the critical first step, particularly as patient outcomes continue to improve with appropriate site-specific and molecular-targeted therapies. We are delighted to see CancerTYPE ID’s superiority in performance compared with the standard-of-care IHC.”

Ding said that this study, together with another recent study showing favorable survival outcomes when physicians use the molecular classifier to direct selection of site-specific therapy, supports the use of CancerTYPE ID as a standardized diagnostic tool in difficult-to-diagnose metastatic cancers.

The study, “Blinded Comparator Study of Immunohistochemical Analysis versus a 92-Gene Cancer Classifier in the Diagnosis of the Primary Site in Metastatic Tumors,” can be accessed here. Preliminary results of the study were reported at the 2012 American Society of Clinical Oncology meeting.

Study: Blinded Comparator Study of Immunohistochemical Analysis versus a 92-Gene Cancer Classifier in the Diagnosis of the Primary Site in Metastatic Tumors

Source: Business Wire

Genomic Health Announces Results from Two Studies Demonstrating Innovations in Next Generation Sequencing From Paraffin Tissue, Enhancing Understanding of Tumor Biology

Genomic Health, Inc. (Nasdaq: GHDX) today announced the results of two studies demonstrating that DNA strand-of-origin information can help further refine the identification of prognostic biomarkers, and that tumor specific gene mutations can be effectively examined using archival fixed paraffin embedded tumor (FPET) tissue, enabling an improved and more practical process of tumor analysis. These new findings were presented at the 14th Annual Advances in Genome Biology and Technology (AGBT) meeting in Marco Island, Fla.

“Our continued research efforts demonstrate the biological and technical capabilities of our advanced next generation sequencing (NGS) methods for biomarker discovery and validation,” said Steven Shak, M.D., chief medical officer and executive vice president for research and development at Genomic Health. “These findings will accelerate the development of future tests based on our ongoing clinical research that combines both whole transcriptome profiling and mutation analysis.”

Novel Next Generation Sequencing and Bioinformatics Methods Enhance Biomarker Discovery

  • Building on study results published in PLoS One — where Genomic Health scientists carried out whole transcriptome RNA-Seq on FPET RNA from a cohort of 136 breast cancer patients — this analysis evaluated the impact of DNA strand-of-origin information on the identification of prognostic biomarkers.

During DNA transcription, only one of the two double-stranded DNA molecules is used as a template for an RNA transcript and protein production. Analytic approaches that do not consider the strand-of-origin of RNA sequencing data can be limited in their accuracy in assigning reads to human genes. Therefore, to perform this study, Genomic Health scientists developed a proprietary NGS and bioinformatics approach to produce a more definite specification of the strand-of-origin of the RNA transcript. The application of this method enabled more precise detection of expressed genes that were significantly associated with breast cancer recurrence, and permitted the identification of 228 additional candidate genes associated recurrence risk in breast cancer.

Enabling Detection of Tumor Specific Mutations Using FPET to Improve Precision of Cancer Diagnosis

  • Reliable differentiation between inherited variations in DNA (germline mutations) and tumor specific variations in DNA (somatic mutations) plays a key role in determining the accuracy and precision of cancer genome sequencing. However, optimally, determination of germline mutations requires the presence of the blood samples in addition to the FPET specimen. This new study showed that by utilizing Genomic Health’s proprietary NGS methods to analyze archival FPET specimens, the company can now reliably detect germline variants and tumor specific mutations when the patient’s blood sample is not available.

As part of this study, 190 frequently mutated cancer genes were sequenced using the Illumina HiSeq™ 2000 System from FPET blocks, analyzing both the patient’s tumor tissue and adjacent non-tumor tissue. Similar sequence analysis was performed on patient-matched blood samples. Readily-available adjacent non-tumor tissue in the FPET specimen was a sufficient alternate source of germline variants to enable the accurate detection of cancer-specific somatic mutations in the tumor.

“Individual patients have an abundance of unique somatic mutations which underscores the heterogeneity of cancer and the importance of gaining better understanding of individual tumor biology for more accurate diagnosis,” said Samuel Levy, Ph.D., Genomic Health’s chief scientific officer. “By applying this technique to work with patients’ archival FPET tissue to identify and account for germline variants, we can learn more from the FPET tumor tissue saved from landmark clinical studies when matched blood samples are not available.”

Source: Genomic Health

MiraDx Highlights Breakthrough Publication Describing a Marker for Resistance to Platinum Treatment in Ovarian Cancer

Mira Dx recently noted the publication of breakthrough research showing that the KRAS-variant acts as a biomarker of poor survival and worse response to treatment for patients with ovarian cancer. Ovarian cancer patients with the KRAS-variant are twice as likely to die of their ovarian cancer, and three times more resistant to standard platinum chemotherapy compared to ovarian cancer patients who do not carry the variant. The KRAS-variant is found in up to 25% of newly diagnosed ovarian cancer patients. Studies are being actively pursued to identify which chemotherapeutic agents work best for these patients.