PharmaShots Interview: Guardant Health's Justin Odegaard Shares Insight on the US FDA's Approval of Guardant360 CDx for Amgen's Lumakras

In an interview with PharmaShots, Justin Odegaard, Vice President of Clinical Development at Guardant Health shares his views on the Guardant360 CDx approval as the first & only liquid biopsy companion diagnostic for Amgen's Lumakras (sotorasib) KRASG12C inhibitor for use in advanced NSCLC.

Shots:

Guardant Health received the US FDA's approval for Guardant360 CDx liquid biopsy for use in conjunction with Amgen's Lumakras (sotorasib) as a KRASG12C inhibitor that received FDA approval simultaneously
Guardant Health liquid biopsy can help identify the 13% of patients with LA or metastatic NSCLC harboring the KRAS G12C mutation
The collaboration between Amgen and Guardant Health provides patients with less-invasive testing and quicker results to determine eligibility for a targeted therapy, like Lumakras (sotorasib)

Tuba: What was the basis for the FDA's approval for the use of sotorasib in patients with KRAS G12C-mutated non-small cell lung cancer?

Justin: The FDA approval of LUMAKRAS is based on results from a subset of patients in CodeBreaK 100, the largest clinical trial conducted to date exclusively for patients with the KRAS G12C mutation. The trial demonstrated favorable efficacy and tolerability in 124 patients with KRAS G12C mutation-positive non-small cell lung cancer (NSCLC) who had disease progression after receiving immunotherapy and/or chemotherapy. In the trial, 960 mg of LUMAKRAS administered orally once-daily demonstrated an overall response rate (ORR) (a proportion of patients with = 30% decrease in the tumor) of 36% (95% CI: 28-45) with 81% (95% CI: 73-87) of patients achieving disease control (percentage of patients who have achieved complete response, partial response and stable disease for more than three months). The median duration of response (DoR) was 10 months. The most common adverse reactions (= 20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. Adverse reactions resulting in permanent discontinuation of LUMAKRAS occurred in 9% of patients.

Tuba: What was the basis for the approval of Guardant360 CDx as the first and only liquid biopsy companion diagnostic for Amgen's LUMAKRAS inhibitor?

Justin: The Guardant360 CDx FDA approval was based on clinical validation data from the CodeBreaK 100 trial evaluating sotorasib in patients with locally advanced or metastatic NSCLC. Patients identified with the KRAS G12C mutation using the Guardant360 CDx demonstrated an objective response rate consistent with those identified using traditional tissue-based biomarker testing.

Tuba: Can you explain the CodeBreaK 100 trial data that validated the use of Guardant360 CDx to detect KRAS G12C-mutated NSCLC and what it showed?

Justin: Guardant360 CDx's FDA approval was based on sotorasib efficacy in subjects from CodeBreaK 100 that tested positive for KRAS G12C mutations by the Guardant360 CDx test. In this population, the observed ORR was highly similar to that observed in the overall drug registration population.

Tuba: Why is Guardant360 CDx so important for oncologists? Why do they turn to it for comprehensive genomic profiling?

Justin: Medical guidelines recommend comprehensive genomic profiling before starting treatment in late-stage and metastatic solid cancers. The Guardant360 CDx test provides comprehensive genomic profiling for patients with solid tumors from a simple blood draw, providing the genomic information necessary for oncologists to make informed treatment decisions in just seven days. This is critical for three reasons: first, comprehensive genomic profiling is mandatory in oncology as it provides the information necessary to properly select therapy and provides patients access to modern targeted agents. Second, Guardant360 CDx provides this information from a simple blood draw, which allows some patients to avoid the pain, risk, expense, and delays of invasive tissue biopsy, while for others for whom this biopsy is not an option, it is the only route by which they can benefit from many modern therapies. Third, by returning results in just seven days, Guardant360 CDx puts this critical information in the hands of the physician before treatment decisions are made. Together, these allow more patients to benefit from modern targeted anti-cancer therapies like LUMAKRAS (sotorasib).

Tuba: What are the key benefits resulting from the collaboration between Amgen and Guardant Health?

Justin: The collaboration between Amgen and Guardant Health provides patients with less-invasive testing and quicker results to determine eligibility for targeted therapy, like LUMAKRAS (sotorasib). This collaboration has led and will continue to lead to more patients being able to access optimal treatment and benefit from modern targeted therapies, and other breakthrough therapies.

Tuba: What is genomic profiling? How has it changed treatment in non-small cell lung cancer?

Justin: Traditionally, medical testing in oncology has assessed a single biomarker at a time. In modern oncology, however, the number and complexity of biomarkers whose status is necessary to know before therapy selection has rendered inadequate such 'one at a time' single biomarker testing approaches. Instead, modern molecular oncology diagnostics now rely on genomic profiling, which is a broad, comprehensive assessment of all relevant biomarkers simultaneously. This allows physicians a complete understanding of patients tumors and allows consideration of all therapeutic options, including those for whom only certain patients are eligible. This is critical as these agents are often associated with markedly improved survival and quality of life relative to non-targeted therapies. Guardant360 CDx was the first liquid biopsy ever approved by the FDA for genomic profiling.

In non-small cell lung cancer specifically, medical guidelines have expanded over the past 10 years and now recommend all patients with metastatic or advanced disease undergo biomarker testing for EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, ERBB2, and KRAS. In total, about half of all patients with NSCLC harbor a targetable driver mutation, each of which represents critical treatment opportunities.

Tuba: Beyond this FDA approval of Guardant360 CDx, what new and important developments are on the horizon for the test?

Justin: Guardant360 CDx offers comprehensive genomic profiling for the standard of care treatment of patients today; however, oncology is advancing rapidly, with more new options for patients being approved every year. Guardant360 continues to evolve to match this innovation, with a 500-gene version of the test already being available for patient care testing today.

Beyond adding new biomarkers, the way in which patients can benefit from liquid biopsies is also evolving. For example, Guardant360's non-invasive approach allows repeated sampling over time, which enables physicians to more rapidly and accurately detect which patients are benefiting from specific therapies and which are not. This has great potential in both clinical care and biopharmaceutical development, and you can expect to hear more from Guardant Health in this area in the near future.

Tuba: Are there any patients support programs for non-small cell lung cancer that have been developed by Amgen and Guardant Health?

Justin: Guardant Health's mission is to expand patient access to the best care possible, regardless of insurance coverage or treatment location. In support of this, Guardant has launched the 'Clear Your View' educational campaign, which aims to provide all oncologists the knowledge and tools necessary to use comprehensive genotyping for their patients. Our hope is that by offering an FDA-approved blood test for this purpose, we can help encourage all clinicians to perform our test to see if their patient has an actionable mutation that can benefit from targeted therapy. Guardant Health also has a robust patient financial assistance program designed to make quality cancer diagnostics accessible to all patients. Any patient can enroll for financial assistance eligibility determination by signing the back of the Test Requisition Form or by contacting Guardant Health Client Services at 855.698.8887 or emailing

clientservices@guardanthealth.com

Amgen is also committed to supporting patients with NSCLC and to helping appropriate patients with affordable access to LUMAKRAS and biomarker testing. Patients, caregivers, and physicians who need support, tools, or resources can contact Amgen Assist360 (1-888-4ASSIST) or visit www.BiomarkerAssist.com to learn more about how to gain access to and save on biomarker testing through the Biomarker Assist program. Amgen also provides patient assistance for its medicines marketed in the U.S. in a variety of ways, including free medicines through the Amgen Safety Net Foundation for qualifying individuals with no or limited drug coverage.

Source: M3 India

About Justin Odegaard:

Dr. Justin Odegaard is currently Vice President of Clinical Development at Guardant Health, where he leads Guardant's clinical trials and companion diagnostic development. Prior to joining Guardant, Dr. Odegaard was Director of molecular pathology at Life code and adjunct attending faculty at Stanford University Hospital. He received his Ph.D. in immunology and his MD from Stanford University, where he later trained in and practiced both surgical pathology and molecular pathology.