Abstract 4572: Preliminary results of perioperative minimal residual disease monitoring using a tumor-informed ctDNA assay in stage II-III breast cancer

作者: Chung, Woosung ; Ahn, Jongseong ; Kang, Eunhye ; Heo, Sunghoon ; Cha, Yongjun ; Han, Wonshik ; Kim, Tae-You ; Kim, Hwang-Phill ; Bang, Duhee ; Lee, Han-Byeol ; Song, Sang-Hyun ; Jung, Jiwoong

AbstractBackground:Detection of minimal residual disease (MRD) via circulating tumor DNA (ctDNA) is a promising biomarker for risk stratification and treatment guidance in cancer. This study evaluated the clinical impact of tumor-informed ctDNA MRD monitoring during the perioperative period in stage II-III breast cancer (BC).Patients and Methods:Patients with stage II-III BC were prospectively enrolled at Seoul National University Hospital (Feb 2023 - Jul 2024). In the neoadjuvant systemic therapy (NST) arm, 20mL of whole blood (WB) was collected at eight perioperative time points: baseline (N00), after one cycle of NST (N01), after completion of NST (N03), and at 1, 6, 12, 24, and 36 months post-surgery. In the adjuvant chemotherapy (AC) arm, WB was collected at seven postoperative time points: 1, 2 months post-AC, and at 6, 12, 24, 36, and 48 months post-surgery. Plasma samples were analyzed using the CancerDetectTM assay (IMBdx, Inc), a personalized tumor-informed MRD detection test. Samples with ≥2 detected mutations were classified as ctDNA+.Results:A total of 231 female patients were enrolled, and 189 met eligibility criteria. This analysis included 111 patients with analyzable WES data, focusing on 103 NST patients. Number of patients analyzed were 103 at N00, 100 at N01, 94 at N03, and 46, 52, 10 at 1, 6, 12 months post-op, respectively. Median age was 51 years (25-72). There were 48 (46.7%) HER2-positive (HER+), 31 (30.1%) triple-negative (TNBC), and 24 (23.3%) hormone receptor (HR)-positive/HER2-negative (HR+/HER2-) BCs. 58 (56.3%) were stage II and 45 (43.7%) were stage III. Median number of target variants from WES was 53 (8-100) and higher in TNBC (67) and HER2+ BC (55) than HR+/HER2- BC (31.5, p = 0.006). Baseline ctDNA positivity was 81.6% (84/103), and ctDNA+ rates by subtype were as follows: 87.1% for TNBC, 83.3% for HER2+ BC, and 70.8% for HR+/HER2- BC (p = 0.281). The positive rate by stage were 77.6% and 86.7% for stage II and stage III, respectively (p = 0.356). Median ctDNA fractions were higher in TNBC (0.186) than HER2+ BC (0.020) or HR+/HER2- BC (0.018, p = 0.031), and higher in stage III (0.125) than stage II (0.012, p = 0.003).After NST completion, the overall pathologic complete response (pCR) rate was 57.3% and ctDNA positivity dropped to 20.2% (19/94), and ctDNA negativity at N03 was associated with higher pCR rates (62.7% vs. 26.3%, p = 0.010). Among N00 ctDNA+ patients, 79.7%achieved clearance after NST, which correlated with higher pCR rates (66.1% vs. 12.5%, p < 0.001). In this subpopulation (median follow-up 13.6, 6.7-19.9), only 4.9% (2/41) of the pCR patients were ctDNA+, no recurrences were reported.Conclusions:Tumor-informed ctDNA assays correlated with NST response in stage II-III BC. Variations in target variants recovered from WES may explain differences in ctDNA positivity by subtype, which should be considered for clinical interpretation and application.Citation Format:Jongseong Ahn, Jiwoong Jung, Yongjun Cha, Sunghoon Heo, Eunhye Kang, Woosung Chung, Hwang-Phill Kim, Duhee Bang, Sang-Hyun Song, Han-Byeol Lee, Wonshik Han, Tae-You Kim. Preliminary results of perioperative minimal residual disease monitoring using a tumor-informed ctDNA assay in stage II-III breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4572.

2025-04-21·Cancer Research

Abstract 3260: Perioperative tumor-informed ctDNA monitoring for minimal residual disease in triple-negative and HER2-positive breast cancer patients

作者: Kim, Tae-You ; Im, Young-Hyuck ; Kim, Hwang-Phill ; Heo, Sunghoon ; Ahn, Jongseong ; Cha, Yongjun ; Song, Sang-Hyun ; Kim, Ji-Yeon ; Shin, Junghoon ; Bang, Duhee

Introduction:Circulating tumor DNA (ctDNA) enables non-invasive monitoring in solid tumors. This study evaluates the prognostic and predictive value of minimal residual disease (MRD) detection using a personalized ctDNA assay during neoadjuvant chemotherapy (NAC) and post-surgical follow-up in triple-negative breast cancer (TNBC) or HER2-positive breast cancer (BC) patients.Methods:Patients with stage IA-IIIC TNBC or HER2-positive BC scheduled for NAC followed by curative surgery were prospectively enrolled. Peripheral blood samples (20 mL) were collected at three time points: before NAC (P0), perioperatively (pre- or one month post-operatively, P1), and one year post-operatively (P2). The CancerDetect™ assay (IMBdx, Inc.), a tumor-informed MRD test, identified patient-specific mutations (up to 100) through whole exome sequencing (WES) of tumor tissue and peripheral blood mononuclear cells. CtDNA positivity was defined as the presence of more than two tumor-derived mutations in plasma.Results:Of 145 patients analyzed (68 TNBC, 77 HER2-positive, median age 49 years), stages included stage I (2.1%), stage II (64.1%), and stage III (33.8%). The median number of mutations identified through WES was 59 (range 9-234), higher in TNBC (71 vs. 50, P = 0.002) but not by stage (P = 0.668). Baseline ctDNA positivity (P0) was 86.9% (median 20 mutations; range 0-97), significantly higher in TNBC (100% vs. 75.3%, P < 0.001) and stage III (95.9% vs. 82.3%, P = 0.021).After NAC, ctDNA clearance occurred in 86.5% of P1-positive patients, with overall ctDNA positivity at P1 dropping to 11.7%, slightly higher in TNBC (14.7% vs. 9.1%, P = 0.314). Pathologic complete response (pCR) rates post-NAC were 55.6%, similar across subtypes and stages. P1 positivity tended to be higher in non-pCR patients (15.6% vs. 7.5%, P = 0.202). CtDNA clearance was associated with higher pCR (60.6%) compared to persistent positive (37.5%, P = 0.106) or persistent negative (42.1%, P = 0.207). For TNBC, P1 positivity was associated with non-pCR (22.6% vs. 5.6%, P = 0.070), unlike HER2-positive BC (9.1% for both).At P2, 90.4% were ctDNA-negative, with positivity in 8.2% (6/73; 4 persistent positives, 2 conversions). At 23 months’ median follow-up, 5 patients developed distant metastases. Persistent positivity at P0-P1 (23.5% vs. 0.8%, P < 0.001) or P1-P2 (75.0% vs. 0%, P < 0.001) was linked to higher recurrence rates.Conclusion:The personalized ctDNA assay detected BC effectively and correlated with subtypes and stages. Post-NAC ctDNA monitoring predicted treatment response and recurrence risk. We are planning longer-term follow-up in the enrolled cohort to better validate its power in recurrence prediction.Citation Format:Yongjun Cha, Junghoon Shin, Jongseong Ahn, Sunghoon Heo, Hwang-Phill Kim, Duhee Bang, Sang-Hyun Song, Young-Hyuck Im, Ji-Yeon Kim, Tae-You Kim. Perioperative tumor-informed ctDNA monitoring for minimal residual disease in triple-negative and HER2-positive breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3260.

2025-04-21·Cancer Research

Abstract 3240: Analytical validation of CancerDetect™ RUO assay: a minimal residual disease detection test that integrates tumor-informed and tumor-agnostic approaches with large-scale mutation monitoring

作者: Bang, Duhee ; Song, Sang-Hyun ; Lee, Hayoon ; Kim, Hwang-Phill ; Heo, Sunghoon ; Ham, Seon-Kyu ; Kim, Tae-You

AbstractBackground:Detection of circulating tumor DNA (ctDNA) has demonstrated clinical utility as a prognostic marker for recurrence by indicating minimal residual disease (MRD). Because the abundance of ctDNA is below the detection limit (LoD) of current tumor genotyping methods (<0.1%), novel technology is required. Currently developed methods adopted personalized tumor genotype informed (tumor-informed) strategy with suboptimal LoD (∼0.01%). Increasing MRD positivity by lowering LoD is required to screen high-risk recurrence patients. Additionally, most of the currently developed MRD test lack clinically actionable information.Methods:A clinically validated personalized large-scale mutation profiling strategy MRD platform, CancerDetectTM, was improved by adding actionable mutation targets across 15 genes recurrently mutated in solid cancers. For analytical validation of personalized mutation regions, well-characterized mixtures of two germline gDNA (NA12891, NA12892) mixture were used, varying mixing ration from 0%, 0.0001%, 0.001%, 0.005%, 0.01%, 0.05% and 0.1%. For analytical validation of the clinically actionable regions, commercially available reference standard (Seraseq® ctDNA MRD Panel Mix) was used with dilution ranged from 0.01% to 0.5%. The panel was designed to target more than 100 different genotype loci (Twist Biosciences).Results:The new iteration of CancerDetectTM integrates personalized tumor-informed large-scale mutation profiling strategy and drug target mutations (tumor-agnostic region) targeting strategy. Results showed that the limit of detection (LoD95) was reached down to 0.001% for tumor-informed region with 99.9% specificity and 0.1% for drug target mutations with 95% specificity. The precision analysis showed 100% and interference test showed that the test performance was not affected by interfering materials (Bilirubin. Wash Buffer) near LoD fraction. Increased sensitivity achieved MRD positivity if 27.2% in a prospective cohort of 551 patients with stage II/III CRC after one month of curative surgery and 45.2% in stage II/III gastric cancer after 3-10 weeks of surgery.Conclusion:The new iteration of CancerDetectTM showed the limit of detection of 0.001% with 99.9% specificity for tumor-informed region and 0.1% with 95% specificity for the tumor-agnostic region. The test result was not affected by the interfering materials and precision analysis showed 100% result. This indicates the new iteration of CancerDetectTM is a robust, sensitive MRD test.Citation Format:Sunghoon Heo, Seon-Kyu Ham, Hayoon Lee, Hwang-Phill Kim, Duhee Bang, Sang-Hyun Song, Tae-You Kim. Analytical validation of CancerDetect™ RUO assay: a minimal residual disease detection test that integrates tumor-informed and tumor-agnostic approaches with large-scale mutation monitoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3240.

项与 IMBdx, Inc. 相关的新闻（医药）

2024-05-22

·BioSpace

Inocras and IMBdx Announce Strategic Partnership to Transform Cancer Patient Care in the U.S.

SAN DIEGO--(BUSINESS WIRE)-- Inocras and IMBdx have announced a partnership aimed at enhancing care for cancer patients in the U.S. Through this partnership, Inocras, a leader in whole genome sequencing diagnostics, and IMBdx, an innovator in liquid biopsy-based diagnostics for cancer, will be able to provide broader offerings for cancer patients and their providers. This press release features multimedia. View the full release here: L to R: Jehee Suh, CEO of Inocras, Tae-You Kim, CEO of IMBdx (Photo: Business Wire) Inocras specializes in cancer profiling using whole genome sequencing (WGS), capturing over 99% of an individual's genomic makeup. This allows for a broader analysis of mutations and complex variations, allowing for deeper insights into a patient's condition. IMBdx has developed a comprehensive portfolio of liquid biopsies for the cancer diagnosis and treatment cycle. The company was recently listed on the KOSDAQ in South Korea. The partnership will focus on Inocras providing IMBdx’s liquid biopsy-based cancer diagnostics in the U.S. market, creating alternatives for patients and their providers when genetic testing from tissue biopsy is not feasible. This joint initiative introduces a new model of patient care, leveraging advanced two technologies in genetic testing - whole genome data and liquid biopsy. "Our collaboration with IMBdx marks a significant step forward in our mission to transform healthcare for cancer and rare disease patients," said Jehee Suh, CEO of Inocras. "We think of patients at the core and are trying to create more options for patients and providers. By combining our strengths, we're not just delivering advanced diagnostic services, we're contributing to creating a pathway to a more effective cancer care journey.” About Inocras Inc: Inocras Inc. (formerly Genome Insight, Inc) is a pioneering provider of whole genome sequencing and analytics for cancer and rare diseases. The company is dedicated to unlocking the potential of genomic data to enable precision health for everyone. For more information about Inocras and our services, please visit Inocras.com. About IMBdx: IMBdx is at the forefront of liquid biopsy technology, developing advanced diagnostic tools that capture and analyze circulating biomarkers to detect and monitor diseases more effectively and non-invasively.

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2023-06-08

·BioSpace

IMBdx Expands Targeted Therapies Agreement Following Successful Evaluation of Blood-Based Genomic Profiling Assay in Prostate Cancer

SEOUL, South Korea, June 8, 2023 /PRNewswire/ -- IMBdx Inc., a premier precision cancer diagnostic company accredited by CAP, announced today its plans to broaden its collaboration with AstraZeneca, a leading global biopharmaceutical company. This expansion will advance the shift from tissue to liquid biopsy, offering more options for metastatic castration-resistant prostate cancer (mCRPC) patients through the AlphaLiquid®HRR test within the PROSPER 2.0 project driven. The collaboration aims to improve accessibility to targeted therapies for mCRPC patients in international markets outside the US. Traditional tissue biopsies in mCRPC patients have high failure rates and require invasive procedures, making liquid biopsy a valuable method for identifying mutations in patients with Homologous Recombination Repair (HRR). AlphaLiquid®HRR, an NGS-based liquid biopsy assay, analyzes plasma ctDNA and reports genomic alterations across all 15 HRR genes. The assay is currently available in various international regions, including Ukraine, Australia, Taiwan, Malaysia, Vietnam, Colombia, Mexico, Lebanon, UAE, Saudi Arabia, Kuwait, and others. As part of the PROSPER 2.0 project, IMBdx and AstraZeneca are jointly exploring how to increase clinician and patient awareness of 1) the clinical utility of ctDNA testing for mCRPC patients to identify those who would benefit from targeted therapies and 2) the detection capability of HRR gene alterations through AlphaLiquid®HRR ctDNA testing. IMBdx has spent over two years developing a best-in-class ctDNA test as a clinical alternative to tissue biopsy for mCRPC patients. A collaborative study with Seoul National University Hospital successfully provided HRR analysis results for 92% of patients using blood samples, demonstrating a high concordance rate between liquid and tissue biopsies. Additionally, the AlphaLiquid®HRR test for the PROSPER 2.0 project has shown a success rate of over 90%. "IMBdx developed the AlphaLiquid® platform, a top-tier performance liquid biopsy test capable of detecting mutations at an exceptionally low level in human blood. We highly value our collaboration with AstraZeneca, which aims to make better clinical decisions that will ultimately benefit more cancer patients and improve their quality of life," said Dr. Tae-You Kim, co-founder and CEO of IMBdx. About IMBdx: IMBdx is an innovative precision oncology company specializing in the diagnosis of tumors through blood samples, committed to converting genomic data into actionable clinical insights by thoroughly examining each patient's unique genomic variations that contribute to cancer development. The company focuses on creating a comprehensive suite of ctDNA tests for profiling, MRD detection, and screening to support patients throughout their cancer journey, while also assisting physicians, researchers, and drug developers in addressing unmet needs. Ultimately, IMBdx aims to detect potential cancer signals before they fully develop. For more information, please visit or follow IMBdx on LinkedIn (@IMBdx).

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100 项与 IMBdx, Inc. 相关的转化医学

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