SERENA-6 Phase III Trial Demonstrates Clinical Value of Guardant360 CDx Test to Detect Emergence of Endocrine Resistance and Inform a Switch in Therapy Before Radiological Disease Progression in Advanced Breast Cancer

• First pivotal trial to use a circulating tumor DNA (ctDNA)-guided approach to detect and treat emerging resistance in 1st-line therapy ahead of disease progression in breast cancer

• Trial showed AstraZeneca’s camizestrant reduced risk of disease progression or death by 56% in patients with advanced HR-positive breast cancer with an emergent ESR1 tumor mutation as detected by Guardant360 CDx

PALO ALTO, Calif.--(BUSINESS WIRE)--Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, today announced that the results of the Phase III SERENA-6 trial - sponsored by AstraZeneca - demonstrate the clinical value of the Guardant360® CDx test in a circulating tumor DNA-guided approach to detect and treat emerging resistance in 1st-line therapy ahead of radiological disease progression in breast cancer. Study results were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago and were published in The New England Journal of Medicine.

SERENA-6 is the first global, double-blind, registrational Phase III trial to use a ctDNA-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression is detected in imaging scans. The novel trial design used ctDNA monitoring with the Guardant360 liquid biopsy test at the time of routine tumor scans to identify patients for early signs of endocrine resistance and the emergence of ESR1 mutations.

“SERENA-6 is a landmark study that is creating a new paradigm using liquid biopsy to enable a switch to a new treatment as soon as you see the cancer showing signs of resistance,” said Helmy Eltoukhy, Guardant Health chairman and co-CEO. “This use of the Guardant360 CDx test highlights how we are pushing the boundaries of what can be done with liquid biopsy in characterizing disease and potential drug efficacy, providing insights that could potentially change clinical practice and improve outcomes in patients with advanced breast cancer.”

Following detection of an ESR1 mutation without radiological disease progression, the endocrine therapy of patients was switched to AstraZeneca’s camizestrant from ongoing treatment with an aromatase inhibitor (AI), while continuing combination with the same cyclin-dependent kinase (CDK) 4/6 inhibitor. The trial demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) in the 1st-line treatment of patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumors had an emergent ESR1 mutation as detected by Guardant360 CDx.

About Guardant360 CDx

The first FDA-approved blood test for complete genomic testing, Guardant360 CDx is approved as a companion diagnostic fur multiple therapies in non-small cell lung cancer. It is also the only FDA-approved companion diagnostic for targeted therapy in advanced breast cancer patients with ESR1 mutations. The test is broadly covered by Medicare and commercial insurers, representing over 300 million lives. For more information, visit the Guardant360 CDx website.

About Guardant Health

Guardant Health is a leading precision oncology company focused on guarding wellness and giving every person more time free from cancer. Founded in 2012, Guardant is transforming patient care and accelerating new cancer therapies by providing critical insights into what drives disease through its advanced blood and tissue tests, real-world data and AI analytics. Guardant tests help improve outcomes across all stages of care, including screening to find cancer early, monitoring for recurrence in early-stage cancer, and treatment selection for patients with advanced cancer. For more information, visit guardanthealth.com and follow the company on LinkedIn, X (Twitter) and Facebook.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the potential utilities, values, benefits and advantages of Guardant Health’s liquid biopsy tests or assays, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect Guardant Health’s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operation” and elsewhere in its Annual Report on Form 10-K for the year ended December 31, 2024, and in its other reports filed with or furnished to the Securities and Exchange Commission thereafter. The forward-looking statements in this press release are based on information available to Guardant Health as of the date hereof, and Guardant Health disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Guardant Health’s views as of any date subsequent to the date of this press release.