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.

3 days ago

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

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

1 month ago

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)

2ms

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.

2 months ago

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)

2ms

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.

2 months ago

Clinical • P1 data • 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 • PF-07248144

2ms

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.

2 months ago

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

2ms

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.

2 months ago

Metastases

HER-2 positive • TP53 mutation • ER positive • PIK3CA mutation • HER-2 mutation • PTEN mutation • ER mutation

Guardant360® CDx

fulvestrant

2ms

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.

2 months ago

Clinical • Clinical data • Circulating tumor DNA • Metastases

HER-2 positive • TP53 mutation • PIK3CA mutation

Guardant360® CDx

Herceptin (trastuzumab)

2ms

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.

2 months ago

Clinical • Real-world evidence • Next-generation sequencing • MSi-H Biomarker • 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

2ms

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%).

2 months ago

Clinical • Circulating tumor DNA • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCND1 (Cyclin D1) • GATA3 (GATA binding protein 3)

ER positive • HER-2 negative • ER positive + HER-2 negative • HER-2 negative + ER positive

Guardant360® CDx

2ms

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.

2 months ago

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

2ms

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.

2 months ago

Circulating tumor cells • Tumor cell

CDH1 (Cadherin 1)

Guardant360® CDx • CELLSEARCH®

2ms

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.

2 months ago

Circulating tumor DNA • Metastases

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)

HR positive • HER-2 negative

Guardant360® CDx

2ms

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.

2 months ago

Circulating tumor DNA • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

HER-2 negative • PIK3CA mutation • HER-2 mutation • ER mutation • ER Y537S • ER D538G • ER Y537N

Guardant360® CDx

everolimus • fulvestrant • Orserdu (elacestrant)

2ms

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.

2 months ago

Review • Liquid biopsy • Circulating tumor DNA • Metastases • Biopsy

HER-2 (Human epidermal growth factor receptor 2)

HER-2 positive • HR positive

Guardant360® CDx

2ms

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.

2 months ago

Clinical • PD(L)-1 Biomarker • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor)

ER positive • HR positive • PIK3CA mutation • PIK3CA E545K • AKT1 E17K • AKT1 mutation • PIK3CA E545 • PGR negative

Guardant360® CDx • MSK-IMPACT

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

2ms

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.

2 months ago

BRCA Biomarker • PARP Biomarker • Circulating tumor DNA

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)

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

Guardant360® CDx

2ms

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.

2 months ago

Clinical • Metastases

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)

HR positive • HER-2 negative • PIK3CA mutation • FGFR1 amplification • ER mutation • AKT1 mutation

Guardant360® CDx

Ibrance (palbociclib) • fulvestrant • ipatasertib (RG7440)

2ms

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.

2 months ago

Clinical • Real-world evidence • BRCA Biomarker • Real-world • 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) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • HER-2 negative • PIK3CA mutation • PTEN mutation • AKT1 mutation

FoundationOne® CDx • Guardant360® CDx

2ms

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.

2 months ago

P1/2 data • Metastases

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)

TP53 mutation • TP53 wild-type

Guardant360® CDx

fulvestrant • Orserdu (elacestrant) • samuraciclib (CT7001)

2ms

Predicting response to capivasertib in AKT1 mutant advanced breast cancer (SABCS 2024)

Allelic imbalance at the AKT1 locus and clonal dominance of the AKT1 mutation were associated with progression free survival (PFS) in plasmaMATCH Cohorts C (capivasertib plus fulvestrant) and D (capivasertib alone) combined. Breast cancers with mutations in AKT1 frequently have allelic imbalance favouring the mutation, resulting in increased expression of mutant transcript. Allelic imbalance of AKT1, and/or clonally dominant AKT1 mutations, were prognostic for significantly greater PFS of patients treated with capivasertib.

2 months ago

Metastases

ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDH1 (Cadherin 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)

TP53 mutation • PIK3CA mutation • AKT1 mutation • AKT1 Q79K

Guardant360® CDx • Prosigna™ Breast Cancer Prognostic Gene Signature Assay

fulvestrant • Truqap (capivasertib)

2ms

Elacestrant vs SOC in ER+, HER2- advanced or metastatic breast cancer (mBC) with ESR1-mutated tumors: ESR1 allelic frequencies and clinical activity from the phase 3 EMERALD trial (SABCS 2024)

Elacestrant demonstrated a significant improvement in mPFS vs SOC in patients with both high and low ESR1 VAF. The clinical benefit and activity of elacestrant vs SOC was maintained regardless of type of ESR1 mutation variant and the abundance/quantity of ESR1 mutations in patients with ER+/HER2- mBC. In all patients with ER+/HER2, ESR1-mut mBC, elacestrant may replace fulvestrant-based combinations, and delay chemotherapy or ADC-based regimens.

2 months ago

Clinical • P3 data • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)

HER-2 negative • HER-2 mutation • ER mutation • ER Y537S • ER D538G • ER Y537N • ER-L

Guardant360® CDx

fulvestrant • Orserdu (elacestrant)

3ms

Genomic landscape of circulating tumor DNA and real-world outcomes in advanced endometrial cancer. (PubMed, Clin Cancer Res)

This study is one of the largest cohorts of ctDNA currently reported in EC. The presence of TP53 mutation and other co-mutations detected by ctDNA have a negative effect on outcomes. This report suggests that ctDNA analysis is feasible and could become a useful biomarker for EC.

3 months ago

Real-world evidence • Journal • Circulating tumor DNA • Real-world • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1)

TP53 mutation • PIK3CA mutation • CCNE1 amplification

Guardant360® CDx

3ms

Updated overall survival and safety data on ripretinib vs. sunitinib in patients with advanced gastrointestinal stromal tumor harboring KIT exon 11 + 17/18 mutations after prior treatment with imatinib: ctDNA analysis by INTRIGUE (DGHO 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 favorable for pts with KIT exon 11 + 17/18 mutations in the ripretinib arm.

3 months ago

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)

3ms

EMERALD: Phase 3 Trial of Elacestrant vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer (clinicaltrials.gov)

P3; Active, not recruiting --> Completed

3 months ago

Trial completion

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)

Guardant360® CDx

fulvestrant • letrozole • anastrozole • exemestane • Orserdu (elacestrant)

3ms

Molecular landscape of ERBB2 alterations in 3000 advanced NSCLC patients. (PubMed, NPJ Precis Oncol)

Notably, EGFR ex20 insertions exhibited greater insertion diversity. Clinical characteristics of EGFR and ERBB2 ex20 NSCLC were similar, characterized by low tumor mutation burden (TMB), a predominant never-smoker population, and a majority of lung adenocarcinoma cases.

3 months ago

Journal • Tumor mutational burden • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden)

HER-2 mutation • TMB-L • HER-2 exon 20 mutation • HER-2 A775 • HER-2 YVMA

Guardant360® CDx

4ms

Genomic Landscape of Advanced Solid Tumors in Middle East and North Africa Using Circulating Tumor DNA (ctDNA) in Routine Clinical Practice. (PubMed, Oncology)

Overall, our findings provide insight into the genomic landscape of individuals with advanced solid organ malignancies from the MENA region and support the role of ctDNA in guiding therapeutic decisions.

4 months ago

Journal • BRCA Biomarker • Circulating tumor DNA • Metastases

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) • 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) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)

BRAF V600E • EGFR mutation • PIK3CA mutation • BRAF V600 • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • ALK fusion

Guardant360® CDx

4ms

ACCRU-GI-2003: Tucatinib Combined with Trastuzumab and TAS-102 for the Treatment of HER2 Positive Metastatic Colorectal Cancer in Molecularly Selected Patients, 3T Study (clinicaltrials.gov)

P2; Trial completion date: May 2029 --> Sep 2024 | Trial primary completion date: May 2025 --> Sep 2024

4 months ago

Trial completion date • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)

MSI-H/dMMR • BRAF mutation • HER-2 amplification • PIK3CA mutation • BRAF V600

Guardant360® CDx

Tukysa (tucatinib) • Lonsurf (trifluridine/tipiracil) • Trazimera (trastuzumab-qyyp)

4ms

GOZILA Study Published in Nature Medicine Shows Patients With Advanced Cancer Who Receive Liquid Biopsy-Guided Treatment Using Guardant360 CDx Survive Twice as Long (Businesswire)

P=NA | N=7,000 | GOZILA (UMIN000029315) | "Guardant Health, Inc...announced the peer-reviewed journal Nature Medicine published results from the SCRUM-Japan GOZILA study confirming that selecting targeted therapy on the basis of Guardant360 CDx liquid biopsy results may significantly extend survival for patients with advanced cancer....The results showed that 24% of participants were able to receive targeted treatment tailored to them based on comprehensive genomic profiling results from the test, which analyzes 74 cancer-related genes. The patients who received targeted treatment guided by liquid biopsy results lived approximately twice as long as those who did not....Patients who received targeted therapy had a median survival of 18.6 months compared to 9.9 months for those who did not."

4 months ago

Clinical data

Guardant360® CDx

4ms

Case series of advanced cancer patients harboring FGFR3-TACC3 fusions detected by comprehensive genomic profiling (ESMO Asia 2024)

Received 3 cycles of pembrolizumab and enfortumab vedotin...Treatment with Erdafitinib, gemcitabine and cisplatin resulted in a partial response...Pembrolizumab with gemcitabine and cisplatin was administered for 4 cycles, but the disease progressed with liver metastasis...Over one year he received many lines of treatment, including sorafenib, gemcitabine and cisplatin, , ramucirumab, nivolumab, and liposomal doxorubicin, lenvatinib durvalumab, and ramucirumab... In clinical practice, ctDNA or tumor NGS can detect rare and actionable FGFR3-TACC fusions in patients with advanced solid tumors that have progressed on standard therapy. Targeted therapy for such fusions can result in clinical benefit.

4 months ago

Clinical • PD(L)-1 Biomarker • Metastases

FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR3-TACC3 fusion

Guardant360® CDx • ACTOnco

Keytruda (pembrolizumab) • Opdivo (nivolumab) • cisplatin • Imfinzi (durvalumab) • gemcitabine • sorafenib • Lenvima (lenvatinib) • Balversa (erdafitinib) • Cyramza (ramucirumab) • Padcev (enfortumab vedotin-ejfv)

4ms

Genomic alterations associated with high Tumor Mutation Burden (TMB-H) status in advanced solid tumors: A single tertiary care oncology center experience from India (ESMO Asia 2024)

TMB-H tumors had a significant enrichment for alterations in genes encoding proteins involved in the DNA repair pathway and growth factor receptor signal transduction. Combining immune checkpoint inhibitors with targeted therapies aimed at specific pathways could be further explored to potentially enhance outcomes for patients with solid tumors.

4 months ago

Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • IO biomarker • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • mTOR (Mechanistic target of rapamycin kinase) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

BRCA1 mutation • TMB-H • MSI-H/dMMR • TMB-L • APC mutation • MTOR mutation

Guardant360® CDx • Guardant360 TissueNext™

4ms

Exploratory ctDNA analyses from first-in-human phase I trial of D3S-001 in patients with advanced solid tumor harboring a KRAS G12C mutation (ESMO Asia 2024)

Conclusions Rapid and sustained molecular response correlated with clinical efficacy and highlighted the importance of TE kinetics of D3S-001. Our data shows that b G12C pos and 100% G12C clearance were associated with better treatment outcome.

4 months ago

Clinical • P1 data • Circulating tumor DNA • Metastases

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1)

KRAS mutation • KRAS G12C • KRAS G12D • STK11 mutation • KRAS G12 • KRAS Q61H

Guardant360® CDx

D3S-001

4ms

Landscape of KRAS mutations in non-small cell lung cancer (NSCLC) patients from Asia and Middle East (AME) using circulating tumor DNA (ctDNA) (ESMO Asia 2024)

Similar to the West, KRAS G12 mutations are the most common, with KRAS G12C nearly twice as common in men than in women. Furthermore, co-existence of EGFR and KRAS mutations occurs approximately 18% KRAS cases representing a diagnostic and therapeutic challenge worthy of further study.

4 months ago

Clinical • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • EML4 (EMAP Like 4) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • SMAD4 (SMAD family member 4) • FANCA (FA Complementation Group A)

KRAS mutation • EGFR mutation • KRAS G12C • EGFR L858R • HER-2 mutation • EGFR exon 19 deletion • EGFR T790M • KRAS G12D • ARID1A mutation • STK11 mutation • KRAS wild-type • RAS wild-type • KRAS G12 • KRAS Q61H • EGFR mutation + KRAS mutation • KRAS Q61 • KRAS Q61L

Guardant360® CDx

4ms

Exploratory biomarker analysis in EGFR mutated NSCLC patients who treated with atezolizumab plus bevacizumab and chemotherapy from phase III ATTLAS trial (ESMO Asia 2024)

Whole genome sequencing (WGS, n=66) and IP analysis (LunitSCOPE, n=148) were performed for both the ABCP and the pemetrexed/carboplatin (PC) arms. The predictive significance of CNAs, analyzed by ctDNA, combined with IP in EGFR-mutated NSCLC patients was observed in patients treated with the ABCP regimen. These results underscore the importance of integrating both genomic and immune profiling to optimize therapeutic strategies.

4 months ago

Clinical • P3 data • Tumor mutational burden • PD(L)-1 Biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • ASXL1 (ASXL Transcriptional Regulator 1) • CDK6 (Cyclin-dependent kinase 6) • STAG2 (Stromal Antigen 2)

EGFR mutation

Guardant360® CDx

Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • pemetrexed

4ms

Landscape of MET activating alterations (METa) in advanced cancers (AC) using circulating tumor DNA (ctDNA) next-generation sequencing (NGS) in Asia and the Middle East (AME) (ESMO Asia 2024)

Co-fusions involved EML4-ALK (1.9%), STRN-ALK (1.2%), and CCDC6-RET (0.7%). Conclusions Comprehensive ctDNA NGS can identify METa and associated co-alterations that may inform therapeutic decisions for patients with AC in AME.

4 months ago

Next-generation sequencing • Circulating tumor DNA • Metastases

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • KIF5B (Kinesin Family Member 5B) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CCDC6 (Coiled-Coil Domain Containing 6) • STRN (Striatin) • CDK6 (Cyclin-dependent kinase 6)

TP53 mutation • EGFR mutation • MET exon 14 mutation • ALK fusion • MET mutation • MET fusion • MET Y1230C • MET Y1230C

Guardant360® CDx

4ms

Landscape of co-occurring OncoKB tier 1/2 alterations in EGFR-mutated lung adenocarcinoma (LUAD) harboring common driver alterations using circulating tumor DNA (ctDNA) next generation sequencing (NGS) in Asia and the Middle East (AME) (ESMO Asia 2024)

Conclusions Comprehensive ctDNA NGS can identify driver EGFR mts and other informative co-alts for patients with LUAD. Frequency and types of such co-alts are mostly similar in AME and other regions.

4 months ago

Next-generation sequencing • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • FGFR2 fusion • EGFR L861Q • EGFR C797S • EGFR G719X • EGFR S768I • EGFR fusion

Guardant360® CDx

4ms

Dacomitinib with or without dose titration in treatment naïve advanced EGFR mutated NSCLC: Primary analysis of the ATORG-003 phase II trial (ESMO Asia 2024)

In the phase III ARCHER1050 trial, both progression-free survival (PFS) and overall survival (OS) were improved with first line dacomitinib compared to gefitinib. Conclusions ATORG-003 prospectively showed dacomitinib with dose titration is a viable strategy in advanced EGFR mutated NSCLC, to maintain efficacy but improve tolerability. Dacomitinib has substantial intracranial activity and high rates of T790M resistance for sequential treatment approaches.

4 months ago

P2 data • Metastases

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M

Guardant360® CDx

gefitinib • Vizimpro (dacomitinib)

4ms

Genomic mutational profile of breast cancer patients from India through comprehensive next-generation sequencing analysis of circulating tumor DNA (ESMO Asia 2024)

Uncovering uncommon PIK3CA and ESR1 alterations beyond hotspot testing. These findings emphasize the clinical utility of ctDNA based comprehensive genomic profiling for treatment guidance.

4 months ago

Clinical • Next-generation sequencing • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDK12 (Cyclin dependent kinase 12)

BRCA1 mutation • MSI-H/dMMR • HER-2 amplification • PIK3CA mutation • ATM mutation • FGFR1 amplification • FGFR2 fusion • ALK fusion • FGFR3 amplification

Guardant360® CDx

4ms

Guardant Health to share data at ESMO 2024 further demonstrating strong performance of its precision oncology technology in multiple advanced tumor types (Guardant Health Press Release)

"Guardant Health, Inc...announced the company and its research collaborators will present data from several studies utilizing Guardant technology to advance precision oncology at the European Society for Medical Oncology Congress (ESMO) in Barcelona, Spain, Sept. 13-17, 2024."

4 months ago

Clinical data

Guardant360® CDx • GuardantINFINITY™ • GuardantREVEAL

4ms

Guardant Health and Policlinico Gemelli announce partnership to establish a dedicated in-house liquid biopsy testing service in Italy (Guardant Health Press Release)

"Guardant Health, Inc...announced a partnership with the Agostino Gemelli University Polyclinic Foundation IRCCS ('Policlinico Gemelli') to establish an in-house liquid biopsy testing service as a part of its diagnostics services within its hospital system. Leveraging Guardant Health’s cutting-edge proprietary digital sequencing platform, this initiative will include on-site analysis of Guardant360 ® CDx liquid biopsy tests directly within the Policlinico Gemelli facilities in Rome, Italy."

4 months ago

Licensing / partnership

Guardant360® CDx

4ms

ctDNA dynamics and mechanisms of acquired resistance in patients treated with osimertinib with or without bevacizumab from the randomised phase II ETOP-BOOSTER trial. (PubMed, Clin Cancer Res)

The differential effect of treatment by smoking was not explained by TP53 mutation or other molecular alterations examined. Molecular mechanisms of acquired resistance were detected but no novel molecular alterations were identified in the combination arm.

4 months ago

P2 data • Preclinical • Journal • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53)

TP53 mutation • EGFR mutation • EGFR L858R • EGFR T790M • EGFR C797S • EGFR L858R + EGFR exon 21 deletion

Guardant360® CDx

Avastin (bevacizumab) • Tagrisso (osimertinib)

5ms

Clinical utility of BRCA and ATM mutation status in circulating tumour DNA for treatment selection in advanced pancreatic cancer. (PubMed, Br J Cancer)

Comprehensive ctDNA profiling provides clinically relevant information regarding HRD status. It can be a practical, convenient option for HRD screening in APC.

5 months ago

Journal • BRCA Biomarker • Circulating tumor DNA • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)

Guardant360® CDx

gemcitabine • albumin-bound paclitaxel

5ms

Guardant Health Japan receives regulatory approval of Guardant360® CDx liquid biopsy as companion diagnostic for amivantamab-vmjw to identify patients with inoperable or recurrent NSCLC harbouring EGFR exon 20 insertion mutations (PRNewswire)

"Guardant Health Japan Corp...announced that the Ministry of Health, Labour and Welfare (MHLW) in Japan has approved Guardant360® CDx as a companion diagnostic to identify EGFR exon 20 insertion mutations in patients with inoperable or recurrent non-small cell lung cancer (NSCLC) for consideration of treatment with amivantamab-vmjw combined with chemotherapy. This approval makes the Guardant360 CDx comprehensive genomic profiling panel the first blood-based companion diagnostic to be approved in Japan for the detection of EGFR exon 20 insertion mutations."

5 months ago

Japan approval

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