International oncology guidelines, such as those from NCCN, ESMO and CSCO, recommend the use of liquid biopsy as an alternative when tumor tissue samples are inaccessible. Currently, most approved NGS IVD kits on ChinaтАЩs market are designed for tumor tissue testing. GeneseeqтАЩs NGS liquid biopsy kit is capable of identifying mutations in multiple key tumor driver genes in a single test with world-leading detection performance, and provides companion diagnostics for a range of targeted therapies. This kit is expected to fill the gap and marks a pioneering step in ChinaтАЩs precision oncology healthcare.

The kit uses advanced non-invasive liquid biopsy testing technology to accurately identify tumor-driving mutations by analyzing circulating tumor DNA (ctDNA) in the blood, without the need for tumor tissue samples. As a valuable complement to traditional tumor tissue testing, it greatly assists clinicians for timely treatment-decision making and drives personalized precision medicine.

Dr. Xiaonan Wang, CTO of Geneseeq, stated, тАЬThis kit is the third NGS IVD product from Geneseeq to enter the NMPA Innovative Medical Device program, following the previous NMPA approvals of the тАШEGFR/ALK/ROS1/BRAF/KRAS/HER2 Mutation Detection KitтАШ and the тАШGeneseeqPrime NGS TMB Testing KitтАШ for tumor tissue testing. From 6 genes to 400+ genes, from tumor tissue to liquid biopsy testing, Geneseeq has always been patient-need driven, continuously exploring the translation of cutting-edge technologies into clinical practice. The successful inclusion of this kit in the Innovative Medical Device program highlighted GeneseeqтАЩs R&D strength and innovation capability in the field of precision medicine. We believe that with the continuous technology innovation and clinical application, more and more patients will benefit from the technological advancements for life quality improvement.тАЭ

The post GENESEEQтАЩS NGS LIQUID BIOPSY KIT MARKS THE FIRST TO ENTER NMPAтАЩS SPECIAL REVIEW AND APPROVAL OF INNOVATIVE MEDICAL DEVICE appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.

Immunotherapy has shown promising results in multiple cancer types, including melanoma, lung cancer, and gastric cancer by harnessing the body’s own immune system to fight cancer. Early-phase clinical trials (PhaseI/II) develop effective immunotherapies by evaluating dose-limiting toxicities and antitumor activity to establish the recommended phase 2 dose (RP2D) for further clinical development. Early changes in circulating tumor DNA (ctDNA) levels over time (kinetics) have been shown to associate with long-term treatment outcomes in patients receiving chemotherapy and targeted therapy. Similar findings have been observed in patients treated with immunotherapy (IO), including immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) in melanoma, lung, and gastric cancers.

In this study, the Princess Margaret Cancer Centre researchers analyzed plasma samples from 81 patients with advanced solid tumors who were being treated with investigational immunotherapy agents in 37 different Phase I/II trials. Using the GeneseeqPrime panel, the researchers evaluated the variant allele fraction (VAF) of mutations in ctDNAs at baseline and before the second cycle of treatment (3-4 weeks) with a sequencing depth of around 5000X. ctDNA was present in 75.3% of the samples and a decreased mean VAF(mVAF) from baseline to pre-cycle 2 was associated with longer progression-free survival and overall survival compared to an increased mean VAF. This overall survival increased significantly when there was a greater than 50% decrease in mean VAF. Interestingly, the researchers did not find significant differences in the median mVAF change rate between patients with hyper progressive disease and those with stable or responding diseases.

тАЬOur results suggest that very early changes in ctDNA levels, as determined by a tumor-naive assay, may be a useful predictor of treatment benefit in phase I/II immunotherapy trials. This approach may help identify responders to immunotherapy at an early stage, allowing for the optimization of treatment strategies and improving patient outcomesтАЭ, says Dr. Qiuxiang Ou, author and associate director of Geneseeq Research Institute.

The post Geneseeq co-publish with UHN on using ctDNA as a prognostic biomarker for immunotherapy appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.

Highlights of these studies include:

• Data on GeneseeqтАЩs new algorithms based on cfDNA fragmentomics features to predict the outcomes of prostate cancer patients as well as to detect lung cancer brain metastases, pulmonary malignancy, and disease progression.
• Two large cohort studies unraveled the landscape of pathogenic/likely pathogenic germline alterations at pan-cancer scale and lung cancer scale.
• Multi-omics analysis of rare cancer populations including fetal adenocarcinoma of the lung and acral melanoma.

List of abstracts that will be presented at the AACR 2023 meeting:

The post Geneseeq to Present 13 Posters at AACR 2023 appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.

This prospective study aims to enroll 405 surgical stage IA-IB NSCLC patients that will be randomized into standard-of-care subgroup and MRD-interfered subgroup with a follow-up period of three years. MRD status is determined by SHIELDING using the plasma samples collected after resection. In the standard-of-care subgroup, patients will receive standard-of-care treatment and follow-up MRD detection every six months. In the MRD-interfered subgroup, the patients are further stratified by MRD status. The MRD-positive patients will receive adjuvant therapy and follow-up MRD detection every three months while the MRD-negative patients will undergo observation and follow-up MRD detection every six months. The primary endpoint is to compare disease-free survival (DFS) between the standard-of-care subgroup and MRD-interfered subgroup, as well as DFS between MRD-positive and MRD-negative patients.

SHIELDING, launched in early 2021, is GeneseeqтАЩs first commercially available MRD product in China for clinical use in the management of early and mid-stage solid tumors.┬аThus far, Geneseeq has released the results of multiple studies evaluating the performance of SHIELDING in different early-stage solid tumors, demonstrating the substantial clinical value of MRD assessment.

тАЬThe initiation of the MOTION study further expands the evidence on clinical values of SHIELDING in real-world settings. WeтАЩre confident that the use of SHIELDING will benefit patients with improved disease outcomesтАЭ, says Dr. Xue Wu, the CEO of Geneseeq Technology Inc.

The post Geneseeq and Collaborators Initiate MOTION Study to Evaluate the Performance of Minimal Residual Disease Test SHIELDINGтДв in Early-stage Lung Cancer appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.

The markings will enable Geneseeq to expand its global business operations and establish new partnerships in the European market.

The MRD detection kit (Shielding Ultra) employs ultra-deep sequencing technology ATG-SEQ to detect low amounts of circulating tumor DNA (ctDNA) in the peripheral blood post-surgical intervention.

For early cancer detection, the in vitro diagnostic kit uses highly sensitive next-generation sequencing-based technology MERCURY to assess multi-omics features of circulating free DNA (cfDNA) and detect tumorigenesis in health population.

In 2022, the council of the European Union has decided to improve cancer screening and strengthening cancer prevention through early detection¹.

“Obtaining the CE marks for both our MRD and MCED kits is an important milestone for Geneseeq to bring personalized liquid biopsy tests to patients worldwide,” said┬аDr. Xue Wu, Geneseeq Technology CEO.

About Geneseeq

Geneseeq is a research-driven company that focus on clinical genetic testing and translational research, covering all cancers and sample types. Geneseeq genomic testing services offer both pan-cancer panels analyzing 400+ genes and cancer-type specific gene panels to help match a patient to the optimal treatment. Last year, Geneseeq announced the progress of a large-cohort, prospective, early cancer screening clinical study named тАЬJinling CohortтАЭ at the Nanjing headquarters earlier. The study will recruit 100,000 participants, providing them with a sensitive yet cost-effective early screening test.

¹https://data.consilium.europa.eu/doc/document/ST-14770-2022-INIT/en/pdf

The post Geneseeq receives CE Marks for MRD and MCED tests. appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.

Being the leading cause of cancer-related death in the world, lung cancer has been difficult to diagnose early in current standard of care settings as most patients are diagnosed at advanced stages, which greatly impacts survival outcomes. Geneseeq has extensively evaluated a multi-dimensional, early cancer detection model based on cfDNA fragmentomics and achieved consistent and excellent performance. In this study, Geneseeq and Jiangsu Cancer Hospital demonstrated the high predictability, stability, and robustness of this model in an early-stage lung cancer population, including patients with extremely low circulating tumor DNA (ctDNA) levels.

The study evaluated plasma cfDNA from a training cohort of 350 non-cancer and 432 cancer participants using shallow whole-genome sequencing (WGS). Multiple cfDNA fragmentomics features, including fragment size coverage (FSC), fragment size distribution (FSD), 6bp end motif (EDM), 6bp breakpoint motif (BPM), and copy number variation (CNV) were tested in the training cohort to enhance the machine learning model;it was then evaluated in three independent cohorts.

The model showed a high┬аarea under the curve (AUC)┬аof┬а0.984,┬а0.987, and┬а0.974┬аfor differentiating lung cancer patients from healthy individuals in the three validation cohorts. The model’s robustness, repeatability and reproducibility were also tested, yielding great performance results. Most notably, the model can identify both squamous cell carcinoma and adenocarcinoma with a 93.3% and 87.0% sensitivity, at a 95.0% specificity. ” It is also sensitive to early pathological features, with a sensitivity of 83.2% at 95.0% specificity for stage I lung cancer, and a sensitivity of 85.0% for tumors less than 10mm.” The model maintained a 75.0% sensitivity in identifying lung cancer patients with low ctDNA (maximum variant allelic fraction of 0.05%) at 0.5X WGS sequencing coverage.

“Geneseeq has been focused on precisely early cancer screening since 2019. The remarkable performance of our early cancer detection model has given us confidence in its real-world and clinical application”, says Dr. Hua Bao, author and the director of Geneseeq Research Institute.

With a series of DECIPHER early cancer detection studies published in high-impact journals, Geneseeq also announced the progress of a large-cohort, prospective, early cancer screening clinical study named “Jinling Cohort” at the┬аNanjing┬аheadquarters earlier this year. The clinical study is jointly led by the┬аNanjing┬аpublic health system, Nanjing Medical University and Geneseeq. The study will recruit 100,000 participants, providing them with a sensitive yet cost-effective early screening test.

Geneseeq is a research-driven company that provides cutting-edge genomic profiling technology to accelerate precision cancer care. Our Canadian and Chinese headquarters focus on clinical genetic testing and translational research, covering all cancer and sample types.

Geneseeq’c clinical laboratory is certified under the Clinical Laboratory Improvement Amendments (CLIA), ISO 15189:2012, and accredited by the College of American Pathologists.

The post Geneseeq Publishes Promising Early Lung Cancer Detection Results in AJRCCM appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.

This study recruited 103 LARC patients who received nCRT at the Fudan University Shanghai Cancer Center from February 2016, to October 2017. The treatment response of the patients was evaluated using pCR status and pathological or MRI tumor regression grade (mrTRG). Plasma samples were collected at baseline (T1), before the 15th (T2), before the 25th (T3) fractions of nCRT and after nCRT (T4). The extracted cell-free DNAs (cfDNAs) were subjected to targeted deep sequencing of 422 cancer-related genes at an average depth of 4000X, and cfDNA 5тАЩ-end motif profiles were extracted to construct an elastic-net logistic regression model to predict non-pCR status before surgery.

Using cross-validation, the constructed model based on the 5тАЩ-end motif profile alone showed a high AUC of 0.90 (95%CI: 0.89-0.91). The combination of the 5тАЩ-end motif and mrTRG further improves the modelтАЩs prediction power, achieving an AUC of 0.92 (95%CI: 0.90-1.00). cfDNA detection and mrTRG detection are two investigated methods that have been used for distinguishing pCR from non-pCR patients. cfDNA detection alone had a high specificity and a low sensitivity while mrTRG1 detection had a high sensitivity with low specificity. Here the combination model based on the combination of the 5тАЩ-end motif and mrTRG showed greatly improved sensitivity and specificity compared to cfDNA detection or mrTRG detection alone. Furthermore, the models based on the 5тА▓-end motif profile alone or in combination with mrTRG consistently demonstrated good predictive ability for patients without detectable cfDNA mutations (AUC 0.94, 95% CI, 0.93тАУ0.95; AUC 0.95, 95% CI, 0.94тАУ0.96).

тАЬThe combination model using 5тАЩ-end motif and mrTRG showed promising performance for predicting pCR in different cohorts, which can be of great value to improve disease outcomes and quality of life for LARC patients.тАЭ, says Dr. Hua Bao, author, and director of Geneseeq Research Institute.

The post Geneseeq study evaluates the clinical value of cell-free DNA 5тАЩ-end motif profile in the prediction of pathological complete response for LARC patients after neoadjuvant chemoradiotherapy appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.

A recent prospective study published in the Drug Resistance Updates, led by Sun Yat-sen University Cancer Center and Geneseeq Technology Inc. demonstrated that the analysis of ctDNA points to drug resistance mechanisms to the combination of vemurafenib, irinotecan, and cetuximab (VIC) in BRAF^V600E mCRC patients, allowing accurate guidance for clinicians in personalized treatment strategies.

This study included 41 BRAF^V600E mCRC patients enrolled in Sun Yat-sen University Cancer Center from July 2018 to June 2020. Tumor tissues and treatment-na├пve plasma samples were collected before treatment. Serial blood samples were collected at the end of every four cycles of VIC treatment until disease progression to dissect the resistance mechanisms and to estimate the prognostic potentials. Tissue and plasma samples were profiled using whole-exome sequencing and the 425-gene Geneseeqprime panel sequencing, respectively.

The study shows that baseline ctDNA BRAF^V600E level was related to a poor prognosis. On the other hand, if ctDNA BRAF is undetected at the first scan, patients showed prominent PFS improvement and dynamic ctDNA BRAF^V600E level changes during/after treatment demonstrated a significant correlation with VIC-related response. Conclusively, NGS-based ctDNA profiling helps detect potential molecular alterations correlated with VIC response and resistance. RNF43 mutations were predominant in pre-treatment plasma samples of patients with long-term clinical benefits, with a response rate as high as 80% and significantly longer PFS after VIC treatment. In those tumors harbouring RNF43 mutations, researchers also observed two tumors achieved clinical responses to immunotherapy. Also, the study shows that acquired gene alterations in DNA damage repair pathways occur in 33% of patients post-VIC treatment, and particularly, patients with this pre-treatment resistance subclones developed inferior responses, along with higher tumor mutation burden both at baseline and progression plasma compared to those without. The researchers identified several additional novel resistance mechanisms to VIC therapy such as TGFBR2 and SMAD4 loss-of-function mutations, and copy-number gains in PTK2, MYC, and GATA6.

These findings highlight the potential of ctDNA surveillance in disease monitor and personalized treatment management in mCRC.

The post Geneseeq study highlights ctDNA monitoring clinical value in colorectal cancer patients resistant to BRAF/EGFR-targeted therapy appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.

This study included 128 stage I-III NSCLC patients who received curative surgical resection at the Jiangsu Oncology Hospital. Primary tumor and lymph node metastasis (LNM) samples were collected from surgeries as the standard of care. Plasma samples were collected pre-surgically, 7 days post-surgically, and every three months thereafter. Both tissue and plasma samples were sequenced using the 425-gene Geneseeqprime panel. A total of 645 tissue samples and 628 plasma samples were included in the analyses. The clonal phylogeny of each patient was reconstructed from multi-region tissue sequencing to aid the ctDNA detection.

Interestingly, patients with lung squamous-cell carcinoma displayed more frequent positive ctDNA results than those with lung adenocarcinoma. The detection rates positively correlated with TNM stages and LNM statuses. Smokers were more frequently ctDNA-positive than non-smokers pre-surgically, but not postsurgically. Notably, postsurgical ctDNA monitoring at as early as seven days after surgeries could indicate a high risk of recurrence (HR = 3.90, 95%CI: 1.85-8.20, P = 0.00011), independently of clinicopathological characteristics (multivariate-Cox: HR = 5.49, 95%CI: 1.86-16.20, P = 0.002). ctDNA detection at 3 months and 6 months could also serve as prognostic markers (3 months – HR = 4.32, 95%CI: 2.06-9.08, P < 0.0001; 6 months – HR = 6.19, 95%CI: 2.44-15.69, P < 0.0001). They remained statistically significant after adjusted for clinicopathological characteristics (multivariate-Cox: 3 months – HR = 4.17, 95%CI: 1.80-9.70, P < 0.001; 6 months – HR = 4.59, 95%CI: 1.68-12.50, P < 0.003). Longitudinal ctDNA detection accurately identified patients at high risk of recurrence (univariate-Cox: HR = 7.59, 95%CI: 3.53-16.32, P < 0.0001; multivariate-Cox: HR = 8.33, 95%CI: 3.59 -19.30, P < 0.001) and covered the majority of recurrence cases (73.5%, 25/34). In these cases, ctDNA MRD detection preceded radiographic relapse by a median of 145 days. The time intervals were similar in LUAD (144 days) and LUSC (150 days)

тАЬctDNA could serve as a promising biomarker for risk of recurrence in NSCLC patients who receive curative surgeries. Longitudinal ctDNA surveillance could reliably predict recurrence, opening a window of ~145 days for timely and optimal disease managementтАЭ, says Dr. Hua Bao, author and director of Geneseeq Research Institute.

The post Interesting findings on ctDNA-based MRD detection in patients with resectable non-small cell lung cancer by Geneseeq appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.

Pan-cancer Studies

Abstract 82P Exploring the prognostic role of DNA damage sensing deficiency for immune checkpoint blockade in diverse cancer types

Study highlight: Immune checkpoint blockade (ICB) produces durable responses on difficult-to-treat tumors, but its effects are heterogeneous on patients. DNA damage response (DDR) is a network of multiple functional pathways to maintain genomic stability, and mutations in DDR genes are a major determinant of response to ICB. However, only a subset of DDR-altered patients benefits from ICB, and their responses vary across cancer types. In this study, the authors retrospectively assessed the prognostic value of pre-defined core DDR pathways using a pan-cancer cohort of 1751 patients derived from cBioPortal TMB/Immunotherapy datasets. The tumor-infiltrating lymphocyte (TIL) scores of 3164 samples derived from TCGA transcriptome datasets were also investigated to evaluate the tumor environment (TME) with different types of DDR statue. The result showed that the prognostic role of DNA damage sensing may provide insights into current biomarkers and help stratify DDR-deficient patients for ICB treatment.

Abstract 1681P Testing the generalizability of cfDNA fragmentomic features across different studies for cancer early detection

Study highlight: The use of cfDNA fragmentomic features has recently shown a strong surge in cancer early detection models. Although many individual studies have demonstrated successful applications in cancer detection, their generalizability remains unclear due to the lack of cross-study validations. A generalized model across studies will allow for robust diagnosis of high-risk individuals. This study evaluated the window-level cfDNA size summary (WINDOW-FSS) feature from the commonly used method profiling the short (100 -150bp) and long (151-220 bp) cfDNA fragments and our in-house developed feature mapping chromosome arm-level fragment size distribution (ARM-FSD) in both lung cancer and pan-cancer models. The cross-study analysis revealed performance variation of models implementing different cfDNA fragmentomic features. The ARM-FSD-based models have consistently demonstrated higher generalizability and robustness in cohorts from diverse sources, highlighting the necessity of cross-study feature verification for future predictive model development.

Lung Cancer Studies:

Abstract 89P Novel resistance mechanisms to second-generation EGFR tyrosine kinase inhibitor afatinib in non-small cell lung cancer

Study highlight: Afatinib, an irreversible pan-ErbB family inhibitor, has demonstrated promising efficacy in non-small cell lung cancer (NSCLC) patients with uncommon EGFR activating mutations. However, besides the acquisition of secondary T790M mutation, other resistance mechanisms to afatinib remained to be explored. This study interrogated the baseline and post-treatment samples from 40 NSCLC patients harboring either EGFR or ERBB2 activating mutations, who had received afatinib as first-line treatment. The authors identified multiple genetic factors associated with afatinib efficacy and resistance as well as genomic characteristics that might serve as biomarkers for afatinib response.

Abstract 107P Systematic characterization of MET activating mutations in non-small cell lung cancer

Study highlight: Alterations in mesenchymal epithelial transition factor (MET) as primary oncogenic drivers or secondary resistance mechanisms to tyrosine kinase inhibitors (TKI) often involve distinct MET mutation subtypes. While MET activating mutations primarily mediates resistance to MET TKIs, increasing evidence suggest that MET activating mutations also exist in the primary tissues. The molecular signatures and clinical relevance of MET activating mutations remain to be elucidated. Here next-generation sequencing data from patients with MET activating mutations were analyzed, and association analyses of genetic and clinical features were conducted. The findings shed light into the diversity of mechanisms underlying TKI resistance and highlight the potential of sequential use of MET TKI.

Abstract 1011P MET and NF2 alterations confer early resistance to first-line alectinib
treatment in ALK-positive non-small-cell lung cancer

Study highlight: The second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), alectinib, has shown prolonged survival in na├пve ALK-rearranged advanced non-small cell lung cancer (NSCLC), with median progression-free survival (PFS) reaching 34.8 months. This study explored the mechanisms of early resistance to alectinib in ALK-rearranged NSCLCs by interrogating the targeted sequencing data from 108 ALK-rearranged NSCLC patients had confirmed clinical relapse on alectinib. The results revealed off-target alterations in MET and NF2 might confer early resistance to 1L alectinib, whereas resistance to 2L alectinib was mainly induced by ALK point mutations. These different mechanisms might be informative in guiding future tailored treatment for ALK-positive NSCLCs.

┬а

The post Geneseeq to present five posters at European Society for Medical Oncology 2022 appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.