Breakthrough Clinical Results

Guardant Health announced that it and its collaborators will present data from over 19 studies at the 2025 ASCO Annual Meeting. These studies highlight the role of Guardant's liquid biopsy tests in various aspects of cancer care, including screening, therapy selection, and recurrence monitoring. Key presentations include a plenary session on the Phase 3 SERENA-6 trial demonstrating the use of Guardant360 CDx in detecting ESR1 mutations in advanced breast cancer, and an oral session on tissue-free epigenomic-based MRD detection in colon cancer using Guardant Reveal. Other studies showcase the Guardant360 Liquid test's ability to identify molecular tumor type and predict the absence of actionable mutations.

Emerging Mechanism of Action

Emerging Mechanisms of Action for Advanced Breast Cancer

Targeted Therapies

Cyclin-dependent kinases (CDK4/6) inhibitors have recently emerged as critical treatments for advanced breast cancer. These agents are now used as first-line treatment for HR+/HER2- advanced breast cancer. The three approved inhibitors are ribociclib, palbociclib, and abemaciclib, with ribociclib showing the most effectiveness in terms of quality-adjusted life years (QALYs). Despite their efficacy in patient subpopulations, no predictive biomarkers have been identified yet. In combination with endocrine treatment, these inhibitors have become standard therapy for estrogen receptor-positive metastatic breast cancer. Studies showed palbociclib demonstrated acceptable efficacy even in heavily treated patients, with median progression-free survival of 7 months and median overall survival of 11 months.

The PI3K/AKT/mTOR Signaling Pathway (PAM pathway) plays a crucial role in breast cancer development and is closely associated with resistance to endocrine therapy in advanced breast cancer. PI3K/AKT/mTOR inhibitors bring significant clinical benefit to advanced breast cancer patients, particularly those with hormone receptor (HR)-positive, HER2-negative disease. FDA-approved treatments include alpelisib (PI3K inhibitor) and everolimus (mTOR inhibitor), with everolimus receiving expanded indication approval from the National Medical Products Administration (NMPA). Combined inhibition of mTOR and estrogen receptor has proven an effective strategy for treating hormone receptor-positive advanced breast cancer.

HER2-Targeted Approaches

HER2-Targeted Therapies represent the cornerstone of treatment for HER2-positive breast cancer, which comprises approximately 20% of breast cancers. These therapies include monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs). Trastuzumab, a monoclonal antibody directed against the Her-2/neu protein, has demonstrated survival benefits in metastatic breast cancer patients.

Trastuzumab emtansine (T-DM1), an antibody drug conjugate, has shown improved outcomes in both early and advanced breast cancer settings. Despite overall survival improvements with these therapies, resistance to treatment remains a significant challenge.

Endocrine and Bone-Targeted Therapies

Aromatase inhibitors (AIs) inhibit estrogen synthesis in peripheral tissues and include anastrozole, exemestane, and letrozole. These agents show a significant survival benefit compared to other endocrine therapies.

Bone-targeted agents (BTAs) such as zoledronic acid and denosumab reduce the incidence of skeletal-related events and delay progression of bone pain, which is crucial for quality of life in advanced disease.

Emerging Approaches

Epigenetically directed therapies targeting histone deacetylases (HDAC) 1 and 3 show promise. Novel HDAC inhibitors like WW437 have demonstrated potent anti-breast cancer ability both in vitro and in vivo by blocking the HDACs-EphA2 signaling axis. EphA2 expression positively correlates with breast cancer progression, and combining WW437 with EphA2 inhibitors shows remarkable effects on breast cancer growth.

The Activin-A Signaling Pathway is hyperactivated in breast cancers, with higher activin-A, phosphoSMAD2, and phosphoSMAD3 levels in advanced disease. Activin-A expression correlates inversely with survival and promotes anchorage-independent growth, epithelial-mesenchymal transition, invasion, angiogenesis, and stemness.

Dual Kinase Inhibition approaches are also emerging. The non-receptor tyrosine kinase c-Abl may regulate responsiveness to lapatinib, and the combination of lapatinib and imatinib (c-ABL kinase inhibitor) may enhance treatment sensitivity.

Next-generation sequencing has identified potentially actionable alterations in fibroblast growth factor receptors (FGFRs) and mutant HER2, offering new targeted approaches for specific patient populations.

Emerging End Points

Drug used in other indications

Based on the provided context, there is no information available about Guardant360 CDx clinical trials for any indications, including advanced breast cancer or any other conditions. The context does not contain any details about Guardant360 CDx being trialed for any medical conditions or any intervention models associated with such trials.