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Genomic Profiling in Cancer: Matching Patients to Precision Trials, Guiding Patients to the Right Treatment

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We recently spoke to Gaurav Singal, Vice President of Data Strategy and Product Development at Foundation Medicine, to learn more about how their SmartTrialsTM technology platform has enabled patients to be rapidly matched to precision trials, based on their unique tumor biomarkers. Gaurav discusses advances in genomic sequencing technologies, the role of genomics in cancer research, and the role genomic profiling plays in guiding patients to the right treatment. 

Could you comment on the increasing role genomic insights is playing in cancer?

Gaurav Singal (GS): Insights into cancer genomics from genomic sequencing technologies have the potential to impact the entire cancer ecosystem. Because of these advances, we are beginning to see cancer treatments today that are guided more by the genomic alterations in a given tumor, rather than where that tumor started in the body. The landmark approval of pembrolizumab for microsatellite-high (MSI-H) tumors regardless of location in the body is a prime example of this shift toward biomarker-driven treatment. Other medicines currently in development are also beginning to follow this approach.

Genomic insights are also enhancing biomarker-driven research, aiding in clinical trial enrollment and helping to maximize the success of these trials. In fact, more than 50% of pipeline therapies are expected to have a biomarker (IIHI Oncology Trend Report 2015).

The value of being better able to predict the likelihood of a therapy being effective is increasingly being recognized by regulators. In November, our FoundationOne CDx test became the first comprehensive genomic profiling assay for all solid tumors that incorporates multiple companion diagnostics to be approved by the Food and Drug Administration (FDA). And, through a National Coverage Determination (NCD) for NGS testing, FoundationOne CDx has national coverage for qualifying Medicare and Medicare Advantage patients across all solid tumors. This was part of a groundbreaking “parallel review” that expedited the decision through agency collaboration between the FDA and the Centers for Medicare and Medicaid Services (CMS).

What genomic biomarkers are used in profiling tumors?

GS: There have been hundreds of cancer-related genomic alterations identified using genomic sequencing technology, and we continue to discover more. For example, mutations in BRCA in breast cancer or EGFR in lung cancer shaped how we diagnose and treat these forms of cancer, enabling more precise diagnoses as well as the development of targeted therapies. Since then, advances in genomic sequencing now allow us to probe hundreds of genes in one test (comprehensive genomic profiling (CGP)) versus looking at genes one by one. This has allowed rapid progress in identifying more genes that may be altered in cancer and which may serve as biomarkers of response or therapeutic targets.

These genomic biomarkers are not only influencing diagnosis and treatment in the clinic, they are impacting the development of new therapies. The pan-cancer approval of pembrolizumab for MSI-high tumors, as well as the promising data on larotrectinib presented at the American Society of Clinical Oncology’s Annual Meeting (ASCO) 2017, reflect the importance of such biomarkers for driving new treatments that may work for a broader population of cancer patients.

Today, there are technologies available that measure genomic biomarkers to impact drug development and patient care. FoundationOne CDx is a broad companion diagnostic and comprehensive genomic profiling (CGP) assay – the first and only FDA-approved test of its kind for all solid tumors. It probes more than 300 cancer-related genes and provides microsatellite instability (MSI) and tumor mutational burden (TMB) status. Both MSI and TMB have been shown to predict a patient’s response to immunotherapy in certain cancer types. As more medicines are approved with FDA-approved genomic biomarkers, our goal is for FoundationOne CDx to expand to incorporate these new biomarker-therapy associations, as well.

The FoundationOne CDx platform also includes companion diagnostics for genomic biomarkers such as BRAF, ALK and BRCA alterations that can inform use of targeted therapies. Companion diagnostics included on the FoundationOne CDx platform can provide a direct path to therapy for 17 FDA-approved targeted therapies, including 12 first line treatments across melanoma, lung, ovarian, colon and breast cancer. Additionally, FoundationOne CDx is a CGP test that includes genomic biomarkers to help inform the use of other targeted therapies, including immunotherapies, and is an important tool for physicians that identifies patient opportunities for clinical trial participation. It is also an FDA-approved platform for companion diagnostic development for biopharma companies developing precision therapeutics.

Does David’s story* highlight the possibility that thinking about cancer by area of the body affected is the wrong approach? Is genomic profiling a better way of treating individual tumors?

GS: The field of oncology is rapidly evolving as more and more evidence builds for the role that genomics plays in predicting response to relevant therapies. It is now clear that, at least in some cases, the presence of a genomic mutation, independent of the organ in which the tumor arose, can be the most important factor in identifying which patients are most appropriate to receive a targeted medicine. Recent regulatory and clinical successes for what we call “tumor agnostic” treatment approaches (e.g., pembrolizumab’s FDA approval for MSI-high tumors and positive data presented on Loxo Oncology’s TRK fusion inhibitor, larotrectinib) underscore this emerging trend.

Could you tell us more about the SmartTrials platform and its role in the NCI-MATCH study, a study evaluating the benefit of genomically-guided treatments targeting specific alterations within a person’s tumor, regardless of cancer type?

GS: Selecting a clinical trial can often be challenging for doctors and patients. It is difficult to know which one is right for each unique patient, and sometimes the appropriate trial sites are not near where patients live. This is even more true now than ever before, as new therapies and the trials studying them are targeting specific genomic biomarkers that could be as rare as one percent or less. To find the right trials for these patients – and the right patients for these trials – is a new challenge for the entire field.

We developed our FoundationSmartTrialsTM program to address patient access barriers and also to help our biopharma partners optimize and streamline clinical trial efficiencies by helping to identify new biomarker targets and potentially eligible patients for enrollment who meet specific genomic criteria.

Foundation Medicine is collaborating with the National Cancer Institute (NCI) and ECOG-ACRIN Cancer Research Group to identify and optimize the number of patients eligible for the NCI-Molecular Analysis Therapy Choice (NCI-MATCH) precision trial. If an individual is identified at a site that is participating in the trial who genomically matches one of the arms of the study, an oncologist in our FoundationSmartTrials program reaches out to the treating physician to inform them of the option to enroll the patient in the NCI-MATCH trial if that provider and patient determine it is the best treatment path for them.

We were selected for participation in NCI-MATCH based on the validation, reliability and accuracy of our assays, the ability to review a high volume of patient cases due to the mainstream use of FoundationOne and FoundationOneHeme in clinical care today, and the ability to quickly assign patients to trials and inform clinicians of this information.

Are the biomarkers that SmartTrials uses to link patients to trials purely genomic, or can transcriptomic and proteomic data also be incorporated?

GS: SmartTrials uses data from our existing portfolio of genomic sequencing assays to match patients to clinical trials. Several of these assays include biomarkers of immunotherapy response, including TMB and MSI.

In addition, Foundation Medicine recently announced a comprehensive gene expression profiling (GEP) program to support precision oncology research and development. GEP may help identify gene expression biomarkers, such as the expression of genes related to immune cells that could predict response to treatments, such as immunotherapy. This program builds on Foundation Medicine’s existing DNA and RNA sequencing platforms, and will initially provide research-use only GEP for its biopharma partners.

*David is a prostate cancer patient. David’s genomic testing results guided him to a clinical trial that wasn’t even studying prostate cancer at the time. But, because the therapy was targeted to his cancer’s specific make-up, David’s enrollment turned out to be life-saving. He is now in complete remission.

Gaurav Singal was speaking to Ruairi MacKenzie and Laura Elizabeth Mason, Science Writers for Technology Networks.