In an interview with PharmaShots, Justin Odegaard, Vice President of Clinical Development and a Laboratory Director at Guardant Health & Yoshiaki Nakamura, Staff Physician in the Department of Gastroenterology and Gastrointestinal Oncology shared their views on the benefits of using the Guardant360 liquid biopsy test in P-II (TRIUMPH) study for HER2-driven metastatic colorectal cancer

Shots:

• The P-II (TRIUMPH) study evaluates pertuzumab + trastuzumab in patients with mCRC harboring HER2 amplification detected by analysis of ctDNA or tissue genotyping. The study is based on (GOZILA) study
• The study showed that the Guardant360 test helps to identify patients with treatment benefits & identify alterations that predict resistance while exploratory analysis evaluates the utility of ctDNA genotyping to predict treatment efficacy, monitor response & identify resistance mechanisms
• The test is 1st FDA-approved liquid biopsy for comprehensive tumor mutation profiling for solid tumor cancers & Guardant360 TissueNext offers another option to oncologists for comprehensive genomic profiling

Tuba: Can you provide an overview of the Guardant360 liquid biopsy test, including its clinical efficacy?

Justin Odegaard: The Guardant360 liquid biopsy provides comprehensive genomic profiling through plasma cell-free DNA. This test can shed light on genomic biomarkers relevant to clinical care through a simple blood draw, rather than requiring the traditional, invasive biopsy to obtain a tissue specimen. In addition, clinicians will get comprehensive genomic results from the Guardant360 liquid biopsy test in seven days, enabling them to start biomarker-informed treatment sooner than with the use of tissue testing. There are a growing number of guideline-recommended biomarkers to be tested in advanced solid tumor cancers that can suggest paired targeted therapy options for patients, often with much higher efficacy and fewer toxicities compared to standard chemo-immunotherapy in those patients.

Tuba: Can you describe how Guardant360 can help in the treatment decisions of HER2-driven metastatic colorectal cancer (CRC)?

Yoshiaki Nakamura: Our study showed the high concordance of identification of HER2 amplification in CRC between a conventional tissue test and Guardant360 and similar efficacy of pertuzumab plus trastuzumab in patients with HER2-amplified CRC confirmed by a tissue test and Guardant360. These strongly indicate that Guardant360 can be utilized for the identification of patients with HER2-amplified CRC who may benefit from anti-HER2 therapy like conventional tissue tests. Our study also suggests that comprehensive circulating tumor DNA (ctDNA) genotyping using Guardant360 may be able to further refine the patient selection by identifying primary resistance determinants.

Tuba: Can you give an overview of the TRIUMPH study? Also, how was the TRIUMPH study impacted by last year’s SCRUM-Japan GOZILA study?

Yoshiaki Nakamura: The SCRUM-Japan GOZILA study is one of the largest ctDNA screening studies in the world. The TRIUMPH study aimed to evaluate the efficacy of dual HER2-blockade for patients with HER2-amplified CRC prospectively confirmed by ctDNA analysis as well as tissue tests. To prospectively identify ctDNA-based HER2-amplied CRC, we needed a large-scale ctDNA screening platform like GOZILA. Therefore, without the GOZILA study, we could not achieve the TRIUMPH study. In addition, the SCRUM-Japan GOZILA study demonstrated the similar efficacy of targeted therapies in clinical trials for patients with specific biomarkers identified by Guardant360 and tissue NGS tests. This finding supports the similar efficacy of dual HER2-blockade in patients with HER2-amplified CRC confirmed by a tissue test and Guardant360 shown in the TRIUMPH study.

Tuba: Can you explain how Guardant360 is different from the other tests on the market?

Yoshiaki Nakamura: Although ctDNA tests on the market seem to have similar performance, Guardant360 is one of the most widely published tests; therefore, it has a lot of evidence. In addition, Guardant360 has a good performance for identification of gene amplification, leading to achieving the TRIUMPH study that treats patients with HER2-amplified CRC confirmed by ctDNA genotyping prospectively.

Tuba: Beyond CRC, what other indications can Guardant360 work for?

Yoshiaki Nakamura: According to previous publications and the indication approved by the FDA, Guardant360 can be used for any type of solid tumor.

Justin Odegaard: The Guardant360 CDx test is the first FDA-approved liquid biopsy for comprehensive genomic profiling for all solid tumor cancers. Apart from colorectal cancer, this includes lung, bladder, breast, cholangiocarcinoma, colorectal, endometrial, gastric and gastroesophageal, GIST, melanoma, ovarian, pancreatic, prostate, and thyroid indications.

Tuba: What other tests have you developed for cancer patients?

Yoshiaki Nakamura: In SCRUM-Japan projects, we are developing multi-omics analysis of tumor tissue and circulating tumor nucleic acids to identify potential patients who may benefit from targeted therapies.

Justin Odegaard: For patients across all stages of cancer, Guardant Health’s blood-based tests are increasingly helping to provide physicians with insights to personalize treatment plans and improve patient outcomes. For patients with advanced or metastatic cancer, the Guardant360 CDx performs complete genomic testing to identify potentially targetable biomarkers. This allows patients with advanced cancers to gain access to appropriate therapies or clinical trials to target the specific genes and proteins, also known as biomarkers, that are causing a person’s cancer cells to grow. Once treatment is started, Guardant360 Response monitors ctDNA levels to see whether a patient is responding to treatment or not and provides oncologists with the insights to consider whether to continue, stop, or explore other treatment options for their patients. For survivors of early-stage cancer, blood-based tests like Guardant Reveal look at circulating tumor DNA levels in a patient’s blood after surgery and help doctors consider whether to deploy a more aggressive treatment regimen, such as chemotherapy or immunotherapy, or continue to monitor the patient with tighter surveillance.

Blood-based tests are also being studied for their accuracy in detecting early signs of cancer in those who are asymptomatic and eligible for cancer screening. As part of its LUNAR Program, Guardant Health is currently evaluating a simple blood test to screen for early signs of colorectal cancer. The test is done via a simple blood draw that can occur in a doctor’s office or in alternate settings by a trained phlebotomist and, therefore, has the potential to dramatically increase screening rates.

Source: Healthwire

About Author:

Dr. Justin Odegaard is vice president of clinical development and a laboratory director at Guardant Health. Dr. Odegaard is a board-certified surgical and molecular pathologist trained at Stanford University, where he remains an adjunct clinical assistant professor of pathology specializing in molecular diagnostic development and circulating tumor DNA. Dr. Odegaard received his MD and Ph.D. from Stanford University School of Medicine

Dr. Yoshiaki Nakamura is a staff physician in the Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East in Kashiwa, Japan. Nakamura received his M.D, from Osaka University, and his Ph.D. from Keio University.

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