Press Release

Large International Cohort of 17 GI Cancer Types Confirms the Unique Clinical Utility of Caris Molecular Intelligence™

Chicago, IL, May 30, 2014 –– Caris Life Sciences, a leading biosciences company focused on fulfilling the promise of precision medicine, announced today the presentation of clinical data at the 50th Annual Meeting of ASCO in which molecular profiling identified numerous potential drug options in patients with various types of gastrointestinal (GI) cancer. Among nine total studies in GI cancer, two notable studies include a 14,000-plus, multi-ethnic international case-study of 17 different types of GI cancer, as well as a separate dataset, a subset of this large cohort, which analyzes nearly 7,000 colorectal cancer (CRC) patients to identify novel potential treatment options that might not otherwise have been considered.
The findings have potentially profound implications for the treatment of cancers of the digestive system, a group of malignancies that account for 17% of all new cases of cancer in the United States (19% in males, 16% in females), and 25% of cancer-related deaths in this country (27% in males, 23% in females).[1] Both clinical studies utilized Caris Molecular Intelligence™, the company’s comprehensive tumor profiling service, which provides valuable treatment information to oncologists and their patients about their unique cancer.
“Our comprehensive, multiplatform approach to molecular profiling is helping oncologists individualize treatment regimens according to the molecular signature of a patient’s tumor,” said Sandeep K. Reddy, M.D., Chief Medical Officer at Caris Life Sciences. “This year’s ASCO presentations by Caris include posters demonstrating how biomarker analysis can inform treatment guidelines and therapeutic decision-making for patients with various types of gastrointestinal cancer, including those of the colon and rectum, stomach, esophagus, bile duct and gallbladder. Given the substantial breadth and depth of these GI studies, we believe these findings should stimulate serious discussion and wider adoption of molecular profiling techniques by the broader oncology community.”
“Molecular Abnormalities of 17 Types of GI Cancer,” presented by Fadi Braiteh, MD, Comprehensive Cancer Centers of Nevada and US Oncology Research. [Abstract/poster #]. Saturday, May 31, 1:15-5:00 pm, [location].
In conjunction with Comprehensive Cancer Centers of Nevada, multi-platform molecular analysis of a large, multi-ethnic, international cohort of 14,207 patients revealed up to 70 molecular abnormalities in tumor samples from 17 sites along the GI tract. The results, derived from the largest repository of data from a single laboratory on the 17 main types of GI cancer, may inform clinical trial design and individualized disease management, according to the investigators, who suggested that protein expression and copy number alterations should be considered together with mutational analysis as a means to refine GI cancer treatment strategies.
The investigators’ analytical tools included gene sequencing (Sanger and next-generation sequencing [NGS]) of up to 44 different genes, immunohistochemistry (IHC) of up to 28 gene products, and gene amplification by chromogenic or fluorescence in situ hybridization (CISH or FISH) of up to eight genes. Hierarchical cluster analysis was performed to determine cancer types that share similar genetic profiles.
Select highlights from this clinical study include:

• Hierarchical cluster analysis showed three distinct tumor type clusters based on biomarker distribution in the gastrointestinal cancers
• Her2 overexpression and amplification are present in esophageal, GEJ, gastric and gallbladder cancers suggesting potential benefit from Her2 targeted therapies
• The majority of KRAS mutations were found in lower GI tract cancers indicating lack of benefit from EGFR antibody therapy
• Activation of PI3K pathway (PTEN loss of expression/ PIK3CA mutation) was found in a majority of GI cancer types, suggesting potential benefit with agents targeting this pathway
• Majority of GI cancers demonstrated overexpressed cMET, suggesting the utility of cMET-targeted therapies that specifically target these oncogenes

“This study, with its large, diverse patient population, including a very large number of patients from the community setting, demonstrates how molecular profiling can be utilized beyond just the university centers, and offers a potential new way to classify GI cancers based on the underlying molecular aberrations instead of by organ and tissue of origin,” said Fadi Braiteh, M.D., Comprehensive Cancer Centers of Nevada and US Oncology Research.  “Our analysis showed that cancers from different GI subtypes may share the same molecular pathway, suggesting that the same types of targeted therapy may be appropriate across GI cancer subtypes, while other types of therapies – whether standard of care or investigational – may be better suited for cancers with more distinct molecular profiles.”
“Molecular profiling of 6,892 colorectal cancer patients to identify potential targeted treatment options” presented by Wafik El-Deiry, MD, PhD and FACP, Penn State Hershey Cancer Institute. [Abstract/poster #]. Saturday, May 31, 8:00 -11:45 am, [location].
In a separate poster presented today, Caris Life Sciences, in conjunction with Penn State Hershey Cancer Institute, reported the identification of distinct biomarker characteristics of metastatic colorectal cancers (CRCs), suggesting novel, unexpected treatment options for this patient population. Working with a subset of the large international GI cancer cohort, and using the same multi-technology approach, 6,892 tumor samples were analyzed to identify potential treatments not usually considered for CRC.
Select highlights from this clinical study include:

• A total of seven different metastatic sites were considered, including the more commonly seen metastases to liver, peritoneum and lung, as well as rarer metastases to ovary, adrenal gland, bone and brain
• Distinct biomarker features were observed in these various metastases of colorectal cancer, suggesting potentially different treatment strategies based on tumor profiling results
  • Her2-targeted therapies may be of particular interest in treating lung metastases based on Her2 overexpression
  • Top2A amplification is the highest in liver metastases, suggesting potential benefit from anthracyclines
  • KRAS mutations are absent in adrenal gland metastasis but more common in brain and lung metastasis than in primary CRC, indicating different responses to EGFR-targeted therapies
  • An overall higher expression of TOPO1 in metastatic sites compared to primary CRC indicates potentially more benefit from irinotecan treatment; while an overall higher expression of MGMT in the metastasis suggest more benefit of using temozolomide in primary CRC

• Tumors with KRAS and BRAF mutations are other difficult-to-treat subgroups of CRC. When compared to KRAS wild type and BRAF wild type patients respectively, KRAS-mutated patients carry significantly higher expression of cMET, while BRAF-mutated patients carry higher PTEN mutations, presenting opportunities for targeted therapies

“Whereas KRAS and BRAF mutations can make colorectal cancer especially aggressive, patients with these mutations have long been thought to have limited treatment options, and there are no detailed treatment guidelines that specifically address various sites of metastasis,” noted Dr. El-Deiry, Chief of Hematology/Oncology at Penn State University and expert on the basic biology and clinical therapy of colorectal cancer. “We identified significant differences among tumors with these mutations, as well as at the different sites of metastasis, providing support for selecting treatments that, in many cases, have not traditionally been considered for patients with colorectal cancer.”
Additional Caris Life Sciences GI datasets include the following ASCO presentations:
Date, Time & Location: Saturday, May 31, 8:00-11:45 am, S Hall A2
General poster session: “PD-1 and PD-L1 in colorectal cancer and their relationship to microsatellite instability status”
Abstract #: 3625
Presenter: Henry Lynch, M.D.
Collaborator: Creighton University
Date, Time & Location: Saturday, May 31, 8:00-11:45 am, S Hall A2
General poster session: “Molecular profiling of bile duct and gallbladder cancer to identify different therapeutic options”
Abstract #: 4097
Presenters: Randall Holcombe, M.D., and Michael A. Morse, M.D.
Collaborators: Icahn School of Medicine at Mount Sinai and Duke University Medical Center
Date, Time & Location: Saturday, May 31, 8:00-11:45 am, S Hall A2
General poster session: “Potential actionable targets in appendiceal cancer detected by immunohistochemistry (IHC) fluorescent in situ hybridization (FISH), and mutational analysis”
Abstract #: 4143
Presenter: Daniel Von Hoff, M.D.
Collaborator: TGen – Virginia G. Piper Cancer Center
Date, Time & Location: Saturday, May 31, 8:00-11:45 am, S Hall A2
General poster session: “Multiplatform molecular profiling of 2,400 pancreatic adenocarcinomas to identify targets for therapeutic intent”
Abstract #: 4136
Presenter: Eileen O’Reilly, M.D.
Collaborator: Memorial Sloan Kettering Cancer Center
Date, Time & Location: Saturday, May 31, 8:00-11:45 am, S Hall A2
General poster session: “Molecular profiling of small bowel adenocarcinomas”
Abstract #: 3647
Presenter: Igor Astsaturov, M.D.
Collaborator: Fox Chase Cancer Center
Date, Time & Location: Saturday, May 31, 8:00-11:45 am, S Hall A2
General poster session: “Profiling of 1,350 neuroendocrine tumors identifies multiple potential drug targets”
Abstract #: 4113
Presenter: Igor Astsaturov, M.D.
Collaborator: Fox Chase Cancer Center

Date, Time & Location: Sunday, June 1, 11:30-12:45 p.m., E Hall D2
Poster highlight session: “Gastrointestinal (non-colorectal): Tumor profiling of 1,306 gastric and esophageal carcinomas reveal different treatment options”
Abstract #: 4017
Presenter: T. Clark Gamblin, M.D.
Collaborator: Medical College of Wisconsin
About Caris Molecular Intelligence™
Caris Molecular Intelligence™, the industry’s leading cancer molecular profiling service, helps oncologists treat cancer smarter by delivering the most potential treatment options for patients. This service has been used by more than 6,000 oncologists to develop individualized and actionable treatment plans for more than 60,000 cancer patients in 59 countries across the globe. Caris Molecular Intelligence integrates the latest relevant panomics data – the combination of genes, proteins, molecular pathways, and unique patient characteristics – from clinical studies in cancer and cancer biology to identify the most clinically actionable drug associations approved by the U.S. Food & Drug Administration or in active clinical trials in the United States. Beyond standard DNA analysis, Caris Molecular Intelligence assesses all relevant biological components, such as RNA, protein expression and gene amplification levels, to provide oncologists with the most treatment options for their patients. Currently, Caris can identify therapeutic guidance for up to 51 drug associations, far exceeding the 19 that can be identified using next-generation sequencing alone. This therapeutic guidance is electronically delivered to the ordering physician in an easy-to-read report that enables development of tailored treatment plans. For more information on Caris Molecular Intelligence, visit www.carismolecularintelligence.com.
 
About Caris Life Sciences
Caris Life Sciences is a leading biosciences company focused on fulfilling the promise of precision medicine. Caris Molecular Intelligence™, the industry’s first and largest tumor profiling service, provides an oncologist with the most potentially clinically actionable treatment options available to personalize care today. Using a variety of advanced and clinically-relevant technologies that assess all relevant biological components of a patient’s cancer, Caris Molecular Intelligence correlates molecular data generated from a tumor with biomarker/drug associations derived from clinical cancer literature. The company is also developing a series of blood tests based on its proprietary Carisome® TOP™ platform, a revolutionary blood-based testing technology for diagnosis, prognosis, and theranosis of cancer and other complex diseases. Headquartered in Irving, Texas, Caris Life Sciences offers services throughout the U.S., Europe, Australia and other international markets. To learn more, please visit www.carislifesciences.com.

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