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    TEST:
    Guardant360® CDx

    Company:
    Guardant Health
    Type:
    FDA Approved
    Related tests:
    4d
    Testing of the Anti Cancer Drugs CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib) in Advanced Stage Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=85, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • BRAF V600K • KEAP1 mutation • NFE2L2 mutation
    |
    Guardant360® CDx • MSK-IMPACT
    |
    sapanisertib (CB-228) • telaglenastat (CB-839)
    9d
    Circulating Tumor DNA in Advanced EGFRex20+ NSCLC: Concordance with Tissue Biopsy, Monitoring of Response, and Resistance to High-Dose Osimertinib. (PubMed, Target Oncol)
    ctDNA analysis tracks variant dynamics and can identify resistance mechanisms in patients with EGFRex20+ NSCLC treated with high-dose osimertinib, offering valuable new insights.
    Journal • Circulating tumor DNA
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR exon 20 insertion
    |
    Guardant360® CDx
    |
    Tagrisso (osimertinib)
    19d
    Measurement of groundwater and contaminant fluxes using a combined system of fractured rock passive flux meter and multiport sampler. (PubMed, Sci Total Environ)
    The results also showed that the selection of appropriate Activated Carbon Felt can improve the accuracy of water flux measurements, and the fraction of tracer remaining on the felt in each experiment exhibited the expected breakthrough curve behaviour. Water flux was measured correctly up to 50 % of tracer loss, but beyond this point, the measurements became less accurate as tracer displacement rate declined.
    Journal
    |
    Guardant360® CDx
    29d
    Clinical Impact of Sub-Clonal RAS/BRAF Alterations in Liquid Biopsies From Patients With Advanced or Metastatic CRC. (PubMed, Clin Colorectal Cancer)
    Consistent with tumor tissue biopsy data, patients with CRC harboring sub-clonal RAS/BRAF mutations as assessed by liquid biopsy may derive benefit from anti-EGFR therapy, warranting further investigation.
    Journal • Liquid biopsy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • KRAS mutation • NRAS mutation • BRAF wild-type • RAS mutation • RAS wild-type • BRAF V600 wild-type
    |
    Guardant360® CDx
    1m
    Real-World Genomic Landscape of Gastrointestinal Cancers in Asia and the Middle East Using Comprehensive Circulating Tumor DNA Next-Generation Sequencing. (PubMed, Oncol Res Treat)
    Our data provide insight into the genomic landscape of patients with gastrointestinal cancers from the AME region using ctDNA analysis. These findings highlight the potential utility of liquid biopsy as a non-invasive tool for characterizing tumor genomic profiles and support its role in clinical practice.
    Journal • Real-world evidence • Next-generation sequencing • BRCA Biomarker • MSi-H Biomarker • Circulating tumor DNA
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset)
    |
    BRAF V600E • MSI-H/dMMR • KRAS G12C • HER-2 amplification • NRAS mutation • BRAF V600 • HER-2 mutation • IDH1 mutation • FGFR2 mutation • FGFR2 fusion • KRAS G12 • IDH mutation + BRAF V600E
    |
    Guardant360® CDx
    1m
    Assessment of Circulating Tumor DNA Burden in Patients With Metastatic Gastric Cancer Using Real-World Data. (PubMed, JCO Precis Oncol)
    We used RWD to demonstrate that high pretreatment ctDNA burden was associated with worse clinical outcomes in a mGC population receiving 1L chemotherapy-based treatments. Our analysis suggests ctDNA burden could be used as a prognostic biomarker for mGC.
    Journal • Real-world evidence • IO biomarker • Circulating tumor DNA
    |
    Guardant360® CDx
    |
    Herceptin (trastuzumab)
    1m
    Liquid and tissue biopsies for identifying MET exon 14 skipping NSCLC: Analyses from the Phase II VISION study of tepotinib. (PubMed, Clin Cancer Res)
    Tepotinib had robust, durable activity in TBx-positive/LBx-negative and TBx-positive/LBx-positive patients. While LBx is a complementary method to TBx for detecting METex14, it may preferentially select patients with higher tumor burden and poorer prognosis. Undetectable METex14 in baseline ctDNA (due to low ctDNA shedding) may define more favorable treatment outcomes.
    P2 data • Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET exon 14 mutation
    |
    Guardant360® CDx • ArcherMET • Oncomine Focus Assay
    |
    Tepmetko (tepotinib)
    2ms
    Brain metastases in patients with metastatic breast cancer and BRCA1/2 mutations in cell-free DNA. (PubMed, Breast Cancer Res Treat)
    A relatively high prevalence of BM in patients with MBC harboring cfDNA somatic BRCA1/2 mutations was observed. CfDNA somatic BRCA1/2 mutations may help identify patients with MBC at risk for BM. To our knowledge, this is the first report linking cfDNA somatic BRCA mutations with BM, and requires further investigation in additional datasets and studies.
    Journal • BRCA Biomarker
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset)
    |
    EGFR mutation • PIK3CA mutation • KIT mutation • BRCA mutation
    |
    Guardant360® CDx
    2ms
    Upfront liquid biopsy in patients with advanced solid tumors who were not feasible for tissue-based next-generation sequencing. (PubMed, Jpn J Clin Oncol)
    In patients with advanced solid tumors for which tissue-based NGS is not feasible, performing upfront liquid biopsy could lead to the detection of actionable alterations and help guide targeted therapies.
    Journal • Liquid biopsy • Next-generation sequencing
    |
    Guardant360® CDx
    2ms
    Serial Circulating Tumor DNA Sequencing to Monitor Response and Define Acquired Resistance to Letrozole/Abemaciclib in Endometrial Cancer. (PubMed, JCO Precis Oncol)
    Baseline and on-treatment ctDNA dynamics may provide an early indication of benefit from letrozole/abemaciclib in EC. ctDNA at the time of progression may identify resistance alterations that may inform subsequent therapy.
    Preclinical • Journal • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1)
    |
    ER positive • MSI-H/dMMR • ESR1 mutation
    |
    Guardant360® CDx • GuardantREVEAL
    |
    Verzenio (abemaciclib) • letrozole
    2ms
    PREVAILctDNA: Preventing Viral Pandemic Associated Risk of Cancer Death Using Less Invasive Diagnostic Tests- Liquid Biopsies (clinicaltrials.gov)
    P=N/A, N=128, Completed, Royal Marsden NHS Foundation Trust | Recruiting --> Completed | N=294 --> 128 | Trial completion date: Dec 2025 --> Jan 2025
    Trial completion • Enrollment change • Trial completion date • Liquid biopsy
    |
    Guardant360® CDx
    2ms
    Frequency and outcomes of BRAF alterations identified by liquid biopsy in metastatic, non-colorectal gastrointestinal cancers. (PubMed, Oncologist)
    Frequency of BRAF GAs, including BRAFV600E, in non-CRC GI cancers detected by liquid biopsy is similar to tissue-based rates and can be reliably used to assess BRAF status. BRAF GAs have mixed prognostic implications on survival for patients with non-CRC GI malignancies that warrant further exploration.
    Journal • Liquid biopsy
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600
    |
    Guardant360® CDx
    3ms
    Liquid biopsy in lung cancer. (PubMed, Jpn J Clin Oncol)
    For cancer prediction recurrence and treatment monitoring, ctDNA analysis can detect MRD earlier than conventional imaging, offering potential benefits for treatment adjustment and early relapse detection. The continuous development and validation of liquid biopsy methods are essential for improving personalized lung cancer treatment strategies.
    Journal • Liquid biopsy • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • EGFR mutation
    |
    Guardant360® CDx • cobas® EGFR Mutation Test v2
    3ms
    Identification of Candidate Alterations Mediating KRASG12C Inhibitor Resistance in Advanced Colorectal and Pancreatic Cancers. (PubMed, Clin Cancer Res)
    Putative resistance alterations are prevalent in PDAC and colorectal cancer and may limit monotherapy efficacy. Identifying these alterations has potential implications in optimal patient selection for targeted therapies and the development of combination therapy strategies to overcome primary resistance.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    Guardant360® CDx
    4ms
    Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLC. (PubMed, JTO Clin Res Rep)
    The prevalence of ESCAT I or II targetable drivers in plasma was significantly higher in patients with adenocarcinoma, 20 pack-year or less smoking history, and abdominal metastases. Our study suggests that the addition of sequential orthogonal biopsy should be considered whenever an ESCAT I or II targetable driver has not been detected by the initial method, including cases with seemingly informative molecular analysis.
    Journal • Next-generation sequencing
    |
    Guardant360® CDx • FoundationOne® Liquid CDx
    4ms
    Avapritinib for the Treatment of CKIT or PDGFRA Mutation-Positive Locally Advanced or Metastatic Malignant Solid Tumors (clinicaltrials.gov)
    P2, N=50, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2025 --> Dec 2026 | Trial primary completion date: Feb 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA mutation
    |
    FoundationOne® CDx • Guardant360® CDx
    |
    Ayvakit (avapritinib)
    4ms
    Round-robin comparison of RET rearrangement detection in ctDNA: A novel method for limited clinical samples. (PubMed, Clin Cancer Res)
    Our results support the utility of ctDNA assays concurrently with tissue testing for detection of translocations, with opportunities to further optimize performance.
    Journal
    |
    RET (Ret Proto-Oncogene)
    |
    RET fusion • RET rearrangement
    |
    Guardant360® CDx • FoundationOne® Liquid CDx
    5ms
    Pembrolizumab in Treating Participants with Unresectable Thymoma or Thymic Cancer (clinicaltrials.gov)
    P1, N=37, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    Guardant360® CDx
    |
    Keytruda (pembrolizumab)
    5ms
    Analytical and Clinical Validation of the Plasma-Based Guardant360 CDx Test for Assessing HER2 (ERBB2) Mutation Status in Patients with Non-Small-Cell Lung Cancer for Treatment with Trastuzumab Deruxtecan in DESTINY-Lung01/02. (PubMed, J Mol Diagn)
    There was a high level of agreement between the Guardant360 CDx test and the ODxT test. The Guardant360 CDx test demonstrated analytical and clinical validity for identifying patients with HER2m NSCLC for T-DXd therapy; results support plasma-based testing when tissue-based testing is not feasible.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 mutation
    |
    Guardant360® CDx • Oncomine™ Dx Target Test • AVENIO ctDNA Expanded Kit
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki)
    5ms
    Impact of Race/Ethnicity on Clinical and Genomic Characteristics, Trial Participation, and Genotype-Matched Therapy among Patients with Metastatic Breast Cancer. (PubMed, Clin Cancer Res)
    Racial/ethnic minority patients were less likely to receive matched therapy. Further research is needed to identify barriers to precision medicine.
    Journal
    |
    Guardant360® CDx
    5ms
    Cell-free tumor DNA analysis in advanced or metastatic breast cancer patients: mutation frequencies, testing intention, and clinical impact. (PubMed, Precis Clin Med)
    The high prevalence of somatic alterations in TP53, PIK3CA, ESR1, and BRCA1/2 genes, identified by ctDNA genotyping, highlights their potential as biomarkers for targeted therapies. Detection of specific mutations affected treatment decisions, such as eligibility for alpelisib, and might further facilitate treatment with e.g. elacestrant or capiversatib in future treatment lines.
    Journal • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    HR positive • HER-2 negative • PIK3CA mutation • EGFR positive
    |
    Guardant360® CDx
    |
    Piqray (alpelisib) • Orserdu (elacestrant)
    5ms
    DGKalpha inhibitor BAY 2862789 FiH trial in advanced solid cancers (ChiCTR2400093606)
    P1, N=81, Jilin Cancer Hospital; Jilin Cancer Hospital
    New P1 trial
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • CD4 (CD4 Molecule)
    |
    EGFR mutation • MSI-H/dMMR • BRAF positive
    |
    FoundationOne® CDx • Guardant360® CDx • Ventana MMR RxDx Panel • OncoMate™ MSI
    |
    BAY 2862789
    5ms
    Dynamic Changes in Circulating Tumor DNA During Immunotherapy for Head and Neck Cancer: SHIZUKU-HN Study. (PubMed, Int J Mol Sci)
    EGFR and PIK3CA amplifications, detectable via ctDNA but missed in tissue biopsies, indicated emerging resistance mechanisms. The SHIZUKU-HN study demonstrates the potential of ctDNA as a dynamic biomarker in HNSCC, offering early insights into treatment efficacy and informing personalized ICI therapy.
    Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • APC (APC Regulator Of WNT Signaling Pathway) • GNAS (GNAS Complex Locus)
    |
    EGFR mutation • BRAF mutation • PIK3CA mutation • PIK3CA amplification • APC mutation • GNAS mutation
    |
    Guardant360® CDx
    6ms
    Testing the Addition of the Anti-cancer Drug, Tazemetostat, to the Usual Treatment (Dabrafenib and Trametinib) for Metastatic Melanoma That Has Progressed on the Usual Treatment (clinicaltrials.gov)
    P1/2, N=58, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Nov 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    BRAF V600E • BRAF V600 • BRAF V600K • EZH2 mutation
    |
    Guardant360® CDx
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • Tazverik (tazemetostat)
    7ms
    Updated overall survival and safety with ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib and harboring KIT exon 11 + 17/18 mutations: ctDNA analysis from INTRIGUE (AIOM 2024)
    In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for pts with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was consistent and more favorable for ripretinib vs sunitinib in these pts. Previously presented at the 2024 ESMO Sarcoma and Rare Cancers Congress.
    Clinical • Circulating tumor DNA • Stroma • Metastases
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase)
    |
    KIT mutation • KIT exon 11 mutation • KIT exon 17 mutation
    |
    Guardant360® CDx
    |
    imatinib • sunitinib • Qinlock (ripretinib)
    7ms
    UPDATED OVERALL SURVIVAL WITH RIPRETINIB VS SUNITINIB IN PATIENTS WITH SECOND-LINE ADVANCED GASTROINTESTINAL STROMAL TUMOR AND KIT EXON 11+17/18 MUTATIONS: CIRCULATING TUMOR DNA ANALYSIS FROM INTRIGUE (CTOS 2024)
    Objective: Ripretinib is a switch-control tyrosine kinase inhibitor approved for patients with gastrointestinal stromal tumor (GIST) who received prior treatment with 3 or more kinase inhibitors, including imatinib. In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for patients with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was consistent and more favorable for ripretinib vs sunitinib in these patients. Previously presented at the 2024 ESMO Sarcoma and Rare Cancers Congress.
    Clinical • Circulating tumor DNA • Stroma • Metastases
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase)
    |
    KIT mutation • KIT exon 11 mutation • KIT exon 17 mutation
    |
    Guardant360® CDx
    |
    imatinib • sunitinib • Qinlock (ripretinib)
    7ms
    Correlation of Mutational Changes in Circulating Tumor DNA with Clinical Outcomes in HER2 Positive Metastatic Breast Cancer (SABCS 2024)
    Molecular alterations identified in ctDNA at progression of disease in HER2 positive MBC can aid in understanding genomic evolution and drift as well as pathways to treatment resistance. This analysis of ctDNA in HER2+ MBC shows that patients with TP53 and PIK3CA co-mutations are shown to have poorer 10-year survival rates, shorter PFS, worse response to Trastuzumab, and overall evidence of more aggressive cancers progressing into visceral metastatic disease. Understanding how the presence of these mutations correlate with resistance to specific therapies can guide individualized treatment decisions on which line of therapies will be most effective for patients with progressive HER2 positive MBC.
    Clinical data • Clinical • Circulating tumor DNA • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR (Fibroblast Growth Factor Receptor)
    |
    HER-2 positive • TP53 mutation • PIK3CA mutation
    |
    Guardant360® CDx
    |
    Herceptin (trastuzumab)
    7ms
    Genomic Profiles of Early Progressors vs Exceptional Responders on CDK4/6i in ER+ HER2- Advanced Breast Cancer (SABCS 2024)
    Pts with HR+ HER2- aBC from a phase II trial of an alternative schedule of palbociclib (palbo alt dosing trial NCT 3007979) and from a retrospective CDK4/6i study were included in this analysis...The majority of these pts received palbo (10/10) paired with letrozole (8/10) and did not have recurrence on adjuvant endocrine therapy (8/10)... Early progression on CDK4/6i is associated with a particularly poor prognosis; however, there are patients with exceptional response to CDK4/6i who may remain on therapy for an extended time. There were variations in the mutation profiles between the two cohorts, though this data set was limited in size. Additional analysis of genomic variants is needed to identify profiles of patients who may significantly benefit from CDK4/6i.
    Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • GNAS (GNAS Complex Locus) • GATA3 (GATA binding protein 3)
    |
    TP53 mutation • EGFR mutation • HR positive • HER-2 negative • PIK3CA mutation • ATM mutation • FGFR1 mutation • AR mutation • HR positive + HER-2 negative
    |
    Guardant360® CDx
    |
    Ibrance (palbociclib) • letrozole
    7ms
    Characteristics of ESR1-Mutant HER2 Positive Metastatic Breast Cancer (MBC) (SABCS 2024)
    Median PFS after detection of ESR1 mutation was 3.2 months (range 1.9 –30.7), with all patients receiving HER2-directed therapy and four patients receiving Fulvestrant... Patients who develop ESR1 mutations in the setting of HER2+ mBC most often had point mutations in L536, E380 and D538, and had high rates of co-mutation with PIK3CA, which may have prognostic implications. To date, clinical trials regarding ESR1 mutations in breast cancer have excluded patients with HER2+ disease. These patients should be included in future studies of ESR1-targeted therapies.
    Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog)
    |
    HER-2 positive • TP53 mutation • ER positive • PIK3CA mutation • HER-2 mutation • PTEN mutation • ER mutation
    |
    Guardant360® CDx
    |
    fulvestrant
    7ms
    PF-07248144, a first-in-class KAT6 inhibitor, in patients with HR+ HER2− metastatic breast cancer: Updated results from phase 1 dose expansion study (SABCS 2024)
    PF-07248144 in combination with fulv demonstrated an acceptable safety profile and promising efficacy in pts with ER+ HER2− mBC post CDK4/6i and ET. Antitumor activity was observed irrespective of ESR1 and PIK3CA/AKT1/PTEN mutation status, endocrine sensitivity or resistance, duration of prior CDK4/6i treatment (12 mos), prior fulvestrant treatment, and 2L or later line therapy. These findings suggest that PF-07248144 in combination with ET may potentially overcome endocrine resistance and CDK4/6i resistance and provide a novel mechanism to address high unmet medical need in HR+ mBC after prior CDK4/6i and ET.
    P1 data • Clinical • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • KAT6A (Lysine Acetyltransferase 6A) • KAT6B (Lysine Acetyltransferase 6B)
    |
    PIK3CA mutation • PTEN mutation • ER mutation • PIK3CA mutation + AKT1 mutation + PTEN mutation
    |
    Guardant360® CDx
    |
    fulvestrant • prifetrastat (PF-07248144)
    7ms
    Point mutations (PM), gene amplifications (GA) and variants of unknown significance (VUS) detected by next-generation sequencing (NGS) in a real-world sample of metastatic breast cancer (MBC) (SABCS 2024)
    NGS of real-world patients reveals a broad spectrum of genomic abnormalities in MBC. TP53 and PIK3CA associate with TNBC and luminal MBC, respectively. Mutations in tumor suppressors are mostly distinct since there are many ways to induce loss-of-function.
    Real-world evidence • Clinical • MSi-H Biomarker • Next-generation sequencing • Real-world • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • CDH1 (Cadherin 1) • FGF4 (Fibroblast growth factor 4) • AURKA (Aurora kinase A) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • GNAS (GNAS Complex Locus) • CCND2 (Cyclin D2) • RAD21 (RAD21 Cohesin Complex Component) • KDM5A (Lysine Demethylase 5A) • ZNF217 (Zinc Finger Protein 217) • FGF23 (Fibroblast Growth Factor 23) • GATA3 (GATA binding protein 3) • ZNF703 (Zinc Finger Protein 703)
    |
    TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • HER-2 expression • PIK3CA H1047R • FGFR1 amplification • CCND1 amplification • FGF3 amplification
    |
    Guardant360® CDx
    7ms
    Extreme ESR1 polyclonality, mutational dynamics and effects on treatment outcomes in patients with ER+ metastatic breast cancer (SABCS 2024)
    In 1 pt, eribulin and abraxane did not have the same effect; ESR1 polyclonality was maintained. One pt with 1 ESR1 clone after 2.5 years of fulvestrant+palbociclib developed 15 additional clones after 1.5 years of an experimental SERD+everolimus. Another pt with 1 ESR1 clone after anastrozole+palbociclib developed 9 additional ESR1 clones after 10 months of AKT inhibition+anastrozole... This is the first investigation of dynamic changes in extreme ESR1 polyclonality in association with treatment outcomes in pts with ER+ MBC. Capecitabine was associated with a decrease in detectable ESR1-mutant clones, while increased polyclonality was found at progression on SERD+everolimus, AKT-inhibitor+AI, and an ADC. Although extreme ESR1 polyclonality is rare, understanding mutational dynamics will improve our understanding of polyclonality more broadly and its impact on treatment resistance.
    Clinical • Tumor mutational burden • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • TMB (Tumor Mutational Burden) • FGFR1 (Fibroblast growth factor receptor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1)
    |
    TP53 mutation • PIK3CA mutation • ER mutation • ER Y537S • ER Y537N
    |
    Guardant360® CDx
    |
    Ibrance (palbociclib) • everolimus • capecitabine • albumin-bound paclitaxel • fulvestrant • Halaven (eribulin mesylate) • anastrozole
    7ms
    Investigating differences in the composition of circulating tumor cells (CTCs) clusters in invasive lobular and ductal carcinoma to decipher lobular breast cancer metastasis (SABCS 2024)
    Further studies including a larger number of pts are needed to validate and better elucidate these findings. The study of CTCCL could shed light on the distinct pattern of metastatic spread of ILC, potentially offering therapeutic opportunities, and serving as a useful prognostic factor.
    Circulating tumor cells • Tumor cell
    |
    CDH1 (Cadherin 1)
    |
    Guardant360® CDx • CELLSEARCH®
    7ms
    Evaluating racial genomic differences in de novo metastatic breast cancer utilizing ctDNA: results from a large multi-center consortium. (SABCS 2024)
    274 of 1134 pts (24.2%) had de novo mBC in the overall cohort, 33 of whom self-identified as Black (12.0%) and 210 as White (76.6%). 26.2% of pts had ctDNA collection prior to any therapy, 24.0% after 1st line therapy, and the remaining pts after 2 or more lines of therapy. In the ER+/HER2- population, there were 193 pts (193/855, 22.6%) with de novo mBC, of whom 29 were Black (15.0%).
    Clinical • Circulating tumor DNA • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCND1 (Cyclin D1) • GATA3 (GATA binding protein 3)
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    ER positive • HER-2 negative • ER positive + HER-2 negative • HER-2 negative + ER positive
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    Guardant360® CDx
    7ms
    Real-World Molecular Profiling After CDK4/6 Inhibition in Advanced Breast Cancer: Analysis of the SOLTI-1903 HOPE Study (SABCS 2024)
    Over two-thirds of pts progressing on CDK4/6i present with ESCAT I-II level alterations detected via tumor or liquid biopsy. Notably, 15-25% of these pts exhibit cooccurring targetable alterations. In our study, the most frequently targeted alteration was PIK3CA mut, due to lack of approval for targeted therapies for other ESCAT I-II alterations in Spain during the study period.
    Real-world evidence • Clinical • BRCA Biomarker • Real-world • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
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    TP53 mutation • BRCA2 mutation • BRCA1 mutation • HER-2 negative • PIK3CA mutation • PTEN mutation • AKT1 mutation
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    FoundationOne® CDx • Guardant360® CDx
    7ms
    Rising ESR1 Mutations in Circulating Tumor DNA (ctDNA) Mediate Endocrine Therapy (ET) Resistance to Everolimus and ET but Retain Sensitivity to Fulvestrant in HR+/HER2- Metastatic Breast Cancer (MBC) (SABCS 2024)
    None of the patients received ESR1-targeted therapy with Elacestrant. Our findings indicate that the level changes of ctDNA ESR1 mutations have implications with regards to treatment sensitivity and resistance to various therapies in patients with HR+/HER2- mBC. These results suggest a potentially effective method for monitoring treatment response and guiding future therapy by providing new insights into targeting ESR1 pathways to overcome resistance.
    Circulating tumor DNA • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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    HER-2 negative • PIK3CA mutation • HER-2 mutation • ER mutation • ER Y537S • ER D538G • ER Y537N
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    Guardant360® CDx
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    everolimus • fulvestrant • Orserdu (elacestrant)
    7ms
    Differential ctDNA-based genomic features of Triple-Negative Metastatic Lobular Breast carcinoma: insights into a rare and poorly understood disease (SABCS 2024)
    Our study highlights distinct genomic features of triple-negative ILC detectable through ctDNA. These findings reinforce the need for improved understanding of TN-ILC to define personalized treatment options for this aggressive and rare subtype.
    Circulating tumor DNA • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • SMAD4 (SMAD family member 4) • CDH1 (Cadherin 1)
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    HR positive • HER-2 negative
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    Guardant360® CDx
    7ms
    BRCA1/2 alterations in circulating tumor DNA: correlation with germline origin and impact on survival in breast cancer. (SABCS 2024)
    The VAF cut-off identified for the likelihood of a germinal mutation detected by ctDNA resulted lower than expected, underlining the importance of a larger germline BC screening, with considerable impact on therapeutic decision making and germline testing of other family members. Further analysis to explore the interplay of different co-mutations with BRCA1/2 will be performed and validation in additional dataset is needed.
    PARP Biomarker • BRCA Biomarker • Circulating tumor DNA
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
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    HER-2 positive • TP53 mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • HR positive • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative • BRCA1 mutation + BRCA2 mutation • HER-2 negative + HR positive + BRCA mutation
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    Guardant360® CDx
    7ms
    A case of sequential alpelisib and capivasertib in a patient with metastatic breast cancer harboring both a PIK3CA and AKT mutations (SABCS 2024)
    Therapies targeting mutations in this pathway approved in conjunction with endocrine therapy include alpelisib, everolimus and capivasertib...She received nab-paclitaxel/atezolizumab for 4 months, letrozole and abemaciclib for 2 months, letrozole alone for 6 months, and letrozole and ribociclib for 6 weeks. Given presence of PIK3CA mutation, 4th line treatment with fulvestrant and alpelisib was planned...After progressing on capecitabine after 2 months, alpelisib with exemestane was initiated...Due to a low ejection fraction despite work with cardiooncology, she was not a candidate for trastuzumab deruxtecan. She progressed on oral cyclophosphamide and methotrexate after 2 months and Sacituzumab govitecan after 3 months...Comprehensive biomarker assessment is needed to identify patients who may benefit from sequential therapies. There is a need for trials comparing therapies that target the PI3K pathway at distinct points, potential sequencing of these therapies, and the optimal sequence strategy.
    Clinical • PD(L)-1 Biomarker • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor)
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    ER positive • HR positive • PIK3CA mutation • PIK3CA E545K • AKT1 E17K • AKT1 mutation • PIK3CA E545 • PGR negative
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    Guardant360® CDx • MSK-IMPACT
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    Tecentriq (atezolizumab) • everolimus • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Piqray (alpelisib) • Verzenio (abemaciclib) • albumin-bound paclitaxel • cyclophosphamide • Kisqali (ribociclib) • fulvestrant • Truqap (capivasertib) • methotrexate • letrozole • Trodelvy (sacituzumab govitecan-hziy) • exemestane
    7ms
    Cyclin-dependent kinase 7 (CDK7) inhibitor samuraciclib combined with selective estrogen receptor degrader (SERD) elacestrant in advanced HR+ breast cancer after CDK4/6i: dose escalation data from the Phase 1b/2 SUMIT-ELA study (SABCS 2024)
    Samuraciclib (CT7001), a once-daily oral CDK7 inhibitor, combined with the SERD fulvestrant had a favorable safety profile and clinical activity in patients with HR+/HER2− advanced breast cancer (BC) previously treated with a CDK4/6i [Coombes, 2023]. The most frequent treatment-related AEs were similar to the known safety profiles from both previous samuraciclib and elacestrant studies. With no drug-drug interactions between the treatments, further study of combination treatment in expansion C4 is supported. Preliminary signs of antitumor activity were observed.
    P1/2 data • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • CDK4 (Cyclin-dependent kinase 4) • CDK7 (Cyclin Dependent Kinase 7)
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    TP53 mutation • TP53 wild-type
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    Guardant360® CDx
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    fulvestrant • Orserdu (elacestrant) • samuraciclib (CT7001)
    7ms
    Genomic predictors of response among patients with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC) receiving the AKT inhibitor (AKTi) ipatasertib combined w/ endocrine therapy & a CDK4/6 inhibitor (CDK4/6i) in TAKTIC trial (SABCS 2024)
    TAKTIC was a phase Ib open-label trial evaluating ipatasertib in combination with fulvestrant, an aromatase inhibitor, or fulvestrant + palbociclib, in participants with HR+/HER2- MBC who received ≥1 line of prior therapy for MBC and had exposure to CDK4/6i (NCT03959891). Genomic insights using NGS suggest that MBC post-CDK4/6i is more susceptible to an AKTi-based treatment with ipatasertib in the presence of a PI3K/AKT/PTEN pathway mutation, whereas alterations in FGFR1 are associated with worse outcomes. This effort is one of very few studies prospectively evaluating mediators of AKTi response, an area of active interest given changes in the therapeutic landscape. The results presented here are hypothesis-generating; future work is underway to further expand upon these data.
    Clinical • Metastases
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CDK4 (Cyclin-dependent kinase 4)
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    HR positive • HER-2 negative • PIK3CA mutation • FGFR1 amplification • ER mutation • AKT1 mutation
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    Guardant360® CDx
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    Ibrance (palbociclib) • fulvestrant • ipatasertib (RG7440)
    7ms
    Circulating tumor DNA (ctDNA) dynamics as a predictor of treatment response: a review of Liquid Biopsy-RECIST (LB-RECIST) criteria in Metastatic Breast Cancer (MBC) (SABCS 2024)
    This analysis confirms the potential of utilizing ctDNA dynamics as a surrogate biomarker for radiographic treatment response. While a 0% cut-off appears to better capture progression compared to a 10% cut-off in both the initial and validation cohorts, prospectives studies are ongoing to standardize and validate LB-RECIST and determine whether optimal VAF cutoffs may be assay and disease context dependent.
    Review • Liquid biopsy • Circulating tumor DNA • Metastases • Biopsy
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    HER-2 (Human epidermal growth factor receptor 2)
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    HER-2 positive • HR positive
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    Guardant360® CDx