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NEXT GENERATION PROFILING FOR PRECISION ONCOLOGY

NEXT GENERATION PROFILING FOR PRECISION ONCOLOGY

Delivering data-driven analytical testing with unprecedented accuracy.

Precision medicine can now be applied where human diseases are further classified into subtypes accordingly to the molecular portrait. The characteristics of certain gene(s) and cluster of genes/protein will have a better prediction on the susceptibility of the disease, the treatment response and prognosis.
Human cancer is one of the most complex dynamic disease. Despite rapid advances, it is still widely researched and debated as to how neoplastic cells progress through carcinogenesis and acquire their metastatic ability.
Recent technological advancements in genomics have paved the way to a deeper understanding of the mechanisms driving the onset and progression of cancer, providing an unprecedented source of information for the investigation of the features determining treatment outcomes. In this aspect, new tools for genome analysis enables us to understand the molecular mechanisms defining pathways that might reasonably influence therapy and response. This development has paved the way for precision medicine which aims to determine unique individuals’ molecular characteristics, select better treatment, and reduce any potential drug adverse reactions. We are thus moving on to an era in which individual genetic profiling will be increasingly relevant in a clinical context.

Molecular biology is a branch of biology that concerns the molecular basis of biological activity between biomolecules in the various systems of a cell, including the interactions between DNA, RNA, proteins and their biosynthesis, as well as the regulation of these interactions.

Molecular pathways and biomarkers molecules are potentially useful for cancer diagnosis because they increase the accuracy of the diagnosis and can be used to identify patients at risk for cancer at an early stage, a critical step in improving the survival rate and reducing the mortality of cancer patients.
A truly comprehensive genomic profiling approach to tumor profiling assesses DNA, RNA and proteins to reveal a molecular blueprint to guide more precise and individualized treatment decisions.

DNA and RNA (courtesy of Wikipedia and International Journal of Molecular Science)

RNA (Ribonucleic acid) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. The rules and roles governing RNA functions have been dramatically expanded during the last two decades with the discovery of the pervasive transcription of eukaryotic genomes and the growing appreciation of non-coding RNA as a plastic and versatile molecule that carries out a myriad of functions ranging from enzymatic catalysis to scaffolding of protein complexes, nucleation of subcellular domains, and the dynamic organization of chromatin.

RNA and DNA are nucleic acids, and, along with lipids, proteins and carbohydrates, constitute the four major macromolecules essential for all known forms of life.

• Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs the synthesis of specific proteins.

 

RNA (Ribonucleic acid) is a nucleic acid present in all living cells essential in various biological roles in coding, decoding, regulation and expression of genes. Its principal role is to act as a messenger carrying instructions from DNA for controlling the synthesis of proteins.

DidYouKnow >>>> The RNA structure is gaining more and more interest in biological research as researchers decipher the tight connections between the functions and structures of non-coding RNAs and increasingly appreciate their versatile roles.

One of the challenges in cancers is the fact that tumors in the same part of the body, or even the same stage might be very different on a molecular or genetic level and may respond very differently to various treatments. In addition, cancers in different parts of the body can respond more similarly to certain treatments than expected. These molecular and genetic similarities and differences are dictated amongst other factors by biomarkers, making tumor profiling a powerful tool when evaluating the patient’s treatment options.

Tumor profiling is a powerful tool when evaluating the patient’s treatment options.

In precision oncology, the target is to find the best treatment for the patient and at the right time. To achieve this, you must analyze the alterations in the patient’s tumor against a large collection of clinical outcomes data and coupled with high quality of testing on a multiplatform approach to determine the best outcome for the patient. Only with a comprehensive assessment analyzing relevant alterations on the DNA, RNA and protein level the outcome for the patient can be optimized.

Only with a comprehensive assessment analyzing relevant alterations on the DNA, RNA and protein level the outcome for the patient can be optimized.

Caris Molecular Intelligence (CMI) pioneered the multiplatform approach utilizing appropriate technology platform to identify clinically relevant and actionable molecular targets for individual patients. This decision support tool helps oncologists with a comprehensive report that provides a summary of all impactful results, and it links all the test results to supporting literature and clinical trials database. The CMI approach incorporates multiple technology platforms as demanded by today’s best clinical practice and offers unique competitive advantages to ordering physicians.
InfoMed was privileged to have an exclusive interview with Caris’s Medical Director International, Dr Schuster Klaus for more insight on the multiplatform profiling and how this whole process is done and the eventual benefits that can be derived for cancer patients.

InfoMed: What has been the motivation to offer this advanced tumor profiling service and will it deliver the clinical benefit expected for cancer patients?
Dr Klaus: Caris Molecular Intelligence® is the first comprehensive tumor profiling service designed to enable the delivery of precision medicine. Our goal is to help patients find the right therapy at the right time to best fight their cancer. Our comprehensive approach to tumor profiling assesses DNA, RNA and proteins to reveal a molecular blueprint that can be used to guide more precise and individualized treatment decisions.

CMI examines DNA, RNA and proteins to decode a patient’s tumor. Currently, CMI covers mutational alterations in 592 genes at the DNA level, 53 genes at the RNA level and more than 12 protein expressions, and provides meaningful, clinically relevant information on immunotherapies, targeted therapies, chemotherapies and clinical trials.

Many studies have shown that aligning the treatment strategy with the molecular test results can help improve outcomes even in advanced cancers.

InfoMed: Can this kind of precision oncology be executed for all types of solid tumor cancers?
Dr Klaus: Yes, CMI is intended for all solid tumors and reveals a patient’s specific cancer biomarkers or targets. CMI helps doctors and their patients:

• identify and navigate among therapies with potential benefit;
• determine drugs with potential lack of benefit (avoiding unnecessary toxicities and costs); and
• match patients to clinical trials.

InfoMed: What kind of tissue sample is needed to profile the tumor?
Dr Klaus: It is of the highest importance to have a high-quality tissue sample on which to run sophisticated tumor profiling and to provide the patients with valid and reliable results. Tissue can be obtained from the surgical removal of the tumor or collected during a biopsy. This tissue is then fixated and preserved in a formalin fixed paraffin embedded block following specific standard procedures.

InfoMed: Who interprets the comprehensive molecular profiling ensuring the highest clinical utility?
Dr Klaus: The profiling consists of several steps: one is the preparation of the tissue, the profiling itself, the evaluation of biomarker results and the final report review. For this service various specialists are involved, such as pathologists, molecular geneticists, bioinformaticians, research scientists and specialized laboratory technicians. In addition, medical experts summarize the report findings afterwards to inform the ordering physician about potential treatment options based upon the results, as well as support the development of a personalized treatment strategy for a specific patient.

InfoMed: Caris Life Sciences constantly updates its profiling service. Please explain why?
Dr Klaus: Caris always uses state-of-the-art-technology and the strongest evidence to provide valid and impactful results that can help improve outcomes for patients. As technology and science evolve, updates to the CMI service are implemented. The Caris team evaluates technical developments and new scientific evidence and discusses this information with external experts to ensure CMI reflects the latest standards.

InfoMed: Why is it important to use multiple technologies to profile tumors?
Dr Klaus: Based on the clinical literature, biomarker and therapeutic associations are analyzed by specific technologies looking for explicit genomic and proteomic aberrations. As such, CMI examines DNA, RNA and proteins using appropriate technology to decode a patient’s tumor and illuminate a clearer path to precision medicine. This technology agnostic, panoramic approach allows our medical teams to more fully understand the biology of the tumor.

InfoMed: Where is the profiling service performed?

Medical students looking through a diagnosis form

Dr Klaus: Molecular testing is performed in Caris’ state-of-the-art, 66,000 sq-ft laboratory in Phoenix, Arizona. The Caris laboratory holds the industry’s strictest quality and compliance accreditations, including ISO 15189, CAP, CLIA, CE Mark and NY State Department of Health.

InfoMed: What do the results of the tumor profiling reveal?
Dr Klaus: The report includes a summary of all findings, including tumor-relevant biomarkers and which therapies, such as immunotherapies, hormone therapies or targeted therapeutics, have increased/decreased likelihood of benefit for the patient.

Details of supporting evidence for each therapy and biomarker are added for the physicians’ information, as well as a list of any ongoing clinical trials that match the patient’s biomarker expression profile (using the company’s proprietary Clinical Trials Connector® service).

InfoMed: Can you briefly highlight the sections of the report?
Dr Klaus: CMI reports are built to maximize clinical utility in an easy-to-interpret format. It contains several sections: the first pages summarize the most important findings and highlight impactful information about mutational alterations and treatment options detected. Details of all findings are displayed on the following pages. A specific section informs the physician about potential clinical trials for the specific patient based on the individual results.

InfoMed: How long does it take to get the results?
Dr Klaus: After the specimen and required paperwork have been received by Caris Life Sciences®, the ordering physician will receive the report in approximately two weeks.

InfoMed: How does the result help doctors in the treatment plan?
Dr Klaus: CMI can aid in revealing impactful information about additional treatment options by analyzing the mutational alterations and protein expressions. This can help the doctor to have an enhanced portfolio of various treatment options, balancing the risks and benefits for each of these therapies and personalizing the treatment recommendation for specific patients.

InfoMed: Can patients request this molecular tumor profiling service?
Dr Klaus: CMI may only be ordered by physicians. If you would like to investigate the possibility of ordering tumor profiling from Caris Life Sciences®, please consult with your oncologist.

InfoMed: Do you have any documentation on the outcomes?
Dr Klaus: From the beginning of the development of CMI, patient outcome has been the main focus and is still the ultimate measurement. As technology and science are evolving and improving, so are outcomes. A recent publication showed improved progression-free survival in more than 50% of patients, whose treatments were aligned with profiling results. ¹Caris collaborates with more than 25 academic centers throughout the world to generate evidence about the influence of CMI on outcomes and drive patient-oriented R&D forward.

InfoMed: Is the profiling service covered by insurance (hospital & surgical plan)?
Dr Klaus: Meetings and negotiations with insurance companies are increasingly ongoing as more and more evidence is available about the added benefit from molecular tumor profiling. In the U.S., CMI is reimbursed by Medicare and Medicaid and also various private insurance companies. Caris supports the application for funding this service with data about improved clinical outcomes, clinical utility and case reports.

Reference:
1) Seeber, A. et al. (in press); Treatment according to a Comprehensive Molecular Profiling leads to an Increase of PFS in Heavily Pretreated Patients with Metastatic Cancer: Data of a pooled Analysis; The Cancer Journal.

Caris Life Sciences®

Caris Life Sciences® is a leading innovator in molecular science focused on fulfilling the promise of precision medicine through quality and innovation, and the world’s leading immunotherapy diagnostic expert. Caris Molecular Intelligence®, the company’s Comprehensive Genomic Profiling Plus (CGP+) molecular testing service, assesses DNA, RNA and proteins, including microsatellite instability (MSI), tumor mutational burden (TMB), mismatch repair status (MMR) and PD-L1, to reveal a molecular blueprint to guide more precise and personalized treatment decisions. Caris’ profiling services are routinely covered by third-party payors, including CMS for Medicare patients. The ADAPT Biotargeting System™, the company’s revolutionary and unbiased profiling platform, is currently being utilized for drug target identification, therapeutic discovery and development, fixed tissue-based companion diagnostics, blood-based cancer screening and biomarker identification. Headquartered in Irving, Texas, Caris Life Sciences offers services throughout the U.S., Europe, Asia and other international markets. To learn more, please visit www.CarisLifeSciences.com.

MUNDIPHARMA

The Mundipharma global network of independent associated companies shares a common purpose to identify and accelerate the development of meaningful medicines that add value for patients and
healthcare providers around the globe.

We have a robust oncology and oncology support portfolio as well as a strong track record of building successful alliances to license, develop and market medicines that improve patients’ lives. We have a strong track record of building successful alliances to license, develop and market medicines that
improve patients’ lives, while also providing attractive options.

Mundipharma Pharmaceuticals Sdn Bhd is the exclusive promoter for Caris Molecular Intelligence in Malaysia and Brunei.

Mundipharma is an independent company and is not an affiliate of Caris Life Sciences or its associates. The molecular profiling and other services described in this material are independently carried out by Caris Life Sciences or its associates.

For more information, please contact:

Mundipharma Pharmaceuticals Sdn. Bhd. (Reg No. 665228K)
A-3-01 Level 3, Block A, PJ8, No. 23 Jalan Barat, Seksyen 8, 46050 Petaling Jaya, Selangor Darul Ehsan, Malaysia
Tel (03) 7946 0606 Fax: (603) 7946 0600

MY-CMI-0987-V1-0119

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