TEST:

GuardantREVEAL

"Guardant Health, Inc...today announced that a jury in the U.S. District Court for the Northern District of California (the “Court”) unanimously found in favor of Guardant Health on all of its claims from its May 2021 lawsuit against Natera, Inc. (Nasdaq: NTRA) (“Natera”) for false advertising and unfair competition. The jury awarded $292.5 million to Guardant Health, including $175.5 million in punitive damages, representing one of the largest false advertising verdicts in history. The jury unanimously rejected all of Natera’s counterclaims."

Our analysis suggests the utility of a tissue-free ctDNA assay in diagnosing minimal residual disease. This could have clinical implications by enabling earlier diagnosis and possibly intervention to delay or prevent metastatic recurrence. We confirm prior studies showing high specificity for recurrence detection with multi-omic plasma-only MRD testing.

Methods The phase II PELOPS trial (NCT02764541) enrolled pts with clinical stage I-III HR+, HER2-negative BC and randomized to NET plus palbociclib or NET alone for 24 weeks prior to surgery; plasma samples were collected at baseline (BL) and prior to surgery (PS)...These results are limited by the sample size but warrant further investigation of the role of ctDNA as a tool to predict sensitivity to ET and long term outcomes. Such a tool could be valuable in tailoring treatment approaches, particularly given the ongoing development of novel ETs and the addition of CDK4/6i in the adjuvant setting.

She remained with no evidence of disease on tucatinib, trastuzumab, and capecitabine for over 19 months but developed severe hand-foot syndrome...The pt's capecitabine dose was increased, and letrozole was added as her resected brain metastasis showed positive progesterone receptor expression... This study describes real-world use and results of a tissue-free monitoring test in early-stage BC. The high QC pass rate (99.9%) and rapid 10-day TAT support the feasibility of a tissue-free assay for MRD detection. Results suggest a potential provider preference for monitoring for patients with stage III BC, TNBC, and HR-/HER2+ BC.

P=N/A, N=120, Active, not recruiting, Grupo Espanol Multidisciplinario del Cancer Digestivo | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2024 --> Apr 2025

In patients with stage II CRC, 71% of tests were ordered within 12 weeks after tumour resection, while for patients with stage III disease, 69% of tests were ordered after completion of all curative-intent treatment. Clinical cases utilizing tissue-free MRD assessment are described.

Follow-up is ongoing to assess the performance of the MRD tests. Conclusions Preliminary real-world experience with a tissue-free test to detect MRD in cfDNA from CRC, BC and NSCLC patients illustrates use patterns in practice with a rapid TAT.

Using tissue-free MRD assessment in routine clinical practice can supplement standard-of-care procedures to determine prognosis and guide therapeutic decisions in patients with early stage CRC.

"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."

"Our data demonstrate the potential clinical utility of ctDNA as a tool to improve management of stage II and higher CRC with a methodology that is non-invasive, accessible, and allows for rapid evaluation to inform clinical decisions."

P=NA| N=NA | "Guardant Health, Inc...announced Clinical Cancer Research, a journal of the American Association for Cancer Research, will publish results today from the COSMOS study confirming the high sensitivity and specificity of the Guardant Reveal blood test in predicting recurrence of colorectal cancer (CRC)....100% of patients were able to undergo evaluation without the need for tissue testing; 98% specificity in samples from patients without recurrence; 81% longitudinal sensitivity for recurrence in stage II or higher colon cancer; 5.3-month median lead time from ctDNA detection to recurrence."

Follow-up is ongoing for all the patients to assess sensitivity and specificity of the MRD test. Conclusions : Preliminary real-world experience with a tissue-free cfDNA MRD test in eNSCLC patients demonstrated similar performance to that reported for tissue-informed assays with fast TAT.

The primary endpoint of NO-CUT trial was met, with the finding that this TNT approach led to a 25.5% NOM rate with a DRFS30 of 96.9%.Supported by grants from Fondazione AIRC ETS (grant IG 2017-20685) and Fondazione Oncologia Niguarda ETS (unrestricted NO-CUT Trial grant).

In postoperative recurrence cases, ctDNA showed a high positive rate from the time of initial diagnosis, suggesting that epigenetic analysis targeting methylation mutations is important in non-TIA cases

P; Tissue-free MRD detection with longitudinal sampling predicts recurrence in stage I-III CRC without need for tissue sequencing. NPV is high supporting ACT de-escalation in patients with ctDNA not detected post-operatively, now being investigated in the UK TRACC Part C study.

"Guardant Health...will present data from 16 studies highlighting the role of Guardant blood tests and real-world data in advancing precision oncology and cancer screening at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting, May 31-June 4 in Chicago...Featured presentations will share data supporting the utility of therapy response monitoring with circulating tumor DNA (ctDNA) using Guardant Infinity and the use of the GuardantINFORM clinical-genomic database to characterize drivers and resistance mechanisms and their association with real-world outcomes in a variety of solid tumor types. Additional studies will present data supporting the application of genomic and epigenomic biomarkers in areas such as minimal residual disease detection and cohort characterization."

We used Guardant REVEALTM assay (v L1.2) to detect ctDNA at 3-4 weeks post-surgery (LB1), after ACT with CAPOX [capecitabine, oxaliplatin (OXA)] (LB2) and post-molecular metastatic treatment with FOLFIRI [5-fluorouracil (5FU), irinotecan (IRI)] or capecitabine (LB3)... Objective changes in avatar tumor growth were mostly consistent with the monitored ctDNA dynamics in matched patients. Avatars models appear to be a faithful proxy of the 'MRD response' to LB-guided adjuvant treatment in CC patients and can be confidently used to unveil mechanistic and functional insights into OXA/IRI resistance mechanisms.

Pts with a history of LNM or poor pre-operative genomic profile were at risk of recurrence despite the absence of MRD after curative-intent resection of CRM.

"Guardant Health, Inc...announced it will present data from nine studies highlighting advances in methylation-based epigenomic analysis for precision oncology at the 2024 American Association for Cancer Research (AACR) Annual Meeting, April 5-10 in San Diego. Multiple poster sessions will report on the utility of using the Guardant Infinity platform across the continuum of cancer care, ranging from predictive histologic subtyping of tumors to cardiac adverse event prediction. Data will also be presented demonstrating strong performance of Guardant Reveal for minimal residual disease (MRD) detection in breast cancer, allowing quantification of ctDNA even in early-stage disease without the need for a tissue specimen."

Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns.

The detection of ctDNA may be a useful biomarker for the management of early-stage cancer patients to identify patients who are at high risk of recurrence. Patients with stage II or III TNBC undergoing neoadjuvant docetaxel and carboplatin chemotherapy on a clinical trial (NCT02124902) followed by surgery were included in this study. ctDNA is detected with a tissue-free MRD assay with high sensitivity and specificity for distant recurrence in early-stage TNBC. Furthermore, the presence of ctDNA during follow-up is a prognostic indicator. Additional prospective studies are needed to assess the clinical utility of ctDNA monitoring in early-stage TNBC.

Detection of ctDNA after adjuvant chemotherapy was highly prognostic in an EBC cohort. ctDNA testing warrants further investigation as a tool to identify EBC patients at high risk for recurrence during follow-up who may benefit from early interventions. Disclosure Statement: The authors declare the following: D.D. and M.C. are employees of Guardant Health.

"Guardant Health, Inc...will present interim data from the COSMOS study supporting the use of Guardant Reveal to predict disease recurrence in patients with early-stage colon cancer at the ASCO 2024 Gastrointestinal Cancers Symposium, January 18-20 in San Francisco....Interim data to be shared at ASCO GI suggest the test is both highly specific (low false positives) and predictive for recurrence, without dependence on a tissue sample....Guardant and its research partners will also present multiple posters at the symposium highlighting the application of Guardant technology in blood-based screening and in identifying potentially targetable mutations in GI cancers, including predictive markers for treatment resistance."

"Guardant Health, Inc...and Hikma Pharmaceuticals PLC...announced an agreement to promote Guardant Health’s portfolio of liquid and tissue biopsy tests for cancer screening, recurrence monitoring and tumor mutation profiling across all solid cancers in countries across the Middle East and North Africa (MENA)...The tests offered include Shield™ for cancer screening and early detection, Guardant Reveal™ for minimal residual disease detection and recurrence monitoring, and Guardant360® and Guardant360 TissueNext™ for comprehensive genomic profiling across all solid cancers."

We show a plasma-only genomic- and methylation-based assay to have sensitive and specific detection of MRD in stage II-III colon cancer. Serial measurement provides superior performance versus one-time measurement at Day 28 post-surgery and detects targetable variants prior to recurrence. >

"Guardant Health, Inc...will present data showing the utility of liquid biopsy tests in the management of breast cancer patients at the San Antonio Breast Cancer Symposium, December 5-9 in San Antonio, Texas. Highlights of the eight poster presentations include the use of blood-based testing to identify actionable biomarkers and predict therapy response in advanced breast cancer, and to detect residual disease and predict recurrence in patients with early-stage breast cancer."

Detection of ctDNA after adjuvant chemotherapy was highly prognostic and demonstrated high specificity in an early-stage breast cancer cohort. Larger, prospective studies are needed to confirm the prognostic value of ctDNA in the post-treatment setting and assess the clinical utility of MRD detection in this population.

P2 | N=140 | PEGASUS (NCT04259944) | "Guardant Health, Inc...announced that initial results from the PEGASUS trial suggest liquid biopsy may be used in post-surgical clinical management to reduce unnecessary toxicity from chemotherapy and improve the response to standard chemotherapy regimens in patients with stage III or high-risk stage II colon cancer...Initial results show that 34% of patients with a positive liquid biopsy result after surgery had the cancer return, while only 10% of patients with a negative result experienced a relapse. Approximately 40% of patients converted from ctDNA-positive to ctDNA-negative after treatment, suggesting treatment efficacy of chemotherapy for some patients."

Results from prospective randomized studies will further define the clinical role of MRD detection in resectable CRC. Evidence for tissue-agnostic MRD assays is building across tumor types with continuous improvements in sensitivity and specificity.

"Digital diagnostics company EDX Medical Group announced...that it will distribute two of Guardant Health's cancer liquid biopsy tests in the UK and the Nordic countries...EDX Medical will distribute the Guardant360 CDx advanced cancer genomic test and the Guardant Reveal test for residual disease and recurrence detection in early-stage cancer to the UK private healthcare sector...It will also distribute Guardant360 CDx to the public and private sectors in Sweden, Denmark, Norway, Finland, and Iceland."

"Guardant Health, Inc...announced...that Geisinger Health Plan now offers coverage for the Guardant Reveal™ minimal residual disease (MRD) test. Guardant Reveal is a blood test that detects circulating tumor DNA (ctDNA) in blood after treatment, including surgery, to help oncologists identify cancer patients with residual or recurring disease who may benefit most from adjuvant therapy or surveillance...This policy decision adds to the payor coverage of Guardant Reveal, which received Medicare coverage in August 2022 and additional commercial payor coverage in July 2023."

P3; The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Written informed consent will be obtained from all eligible patients prior to registration.

Patients with poor genomic profile and positive MRD derived significant benefit from ACT (median RFS, 8.0 m vs. 2.0 m; HR, 0.25 [95% CI, 0.07–0.82]), while no significant benefit was observed in other groups. Conclusions Pretreatment genomic profile and postoperative MRD by ctDNA analysis accurately stratify the prognosis and may guide personalized ACT in pts with resectable CRM.

Conclusions This longitudinal evaluation of a plasma-only methylation based ctDNA assay demonstrates ctDNA detection and dynamic changes in a large EBC cohort. Potential prognostic and predictive applications warrant further evaluation.

Of the 23 LB+ pts receiving FOLFIRI after CAPOX, 12 remained LB+ (52%) among which 6 relapsed, while 11 were converted to LB- remaining relapse-free at the time of analysis (48%), thus suggesting an effect of FOLFIRI in the MRD setting. Conclusions LB may be used to guide the post-surgical clinical management of CC pts by reducing unnecessary toxicity and by improving the response to standard chemotherapy. Ongoing and newly designed randomized trials trials will define the clinical utility of LB for MRD in colon cancer.

"Guardant Health, Inc...announced...that Blue Cross and Blue Shield of Louisiana now offers coverage for the Guardant Reveal™ molecular residual disease (MRD) test. Guardant Reveal is a blood test that detects circulating tumor DNA (ctDNA) in blood after treatment, including surgery, to help oncologists identify cancer patients with residual or recurring disease who may benefit most from adjuvant therapy or surveillance. It was the first blood-only liquid biopsy test commercially available for MRD testing."

P=N/A; Not yet recruiting --> Recruiting

P=N/A; Initiation date: Mar 2023 --> Jun 2023

Support: U10CA180868, -180822; UG1CA189867; GuardantHealth. Clinical trial information: NCT04068103.

P=N/A; The trial will determine whether ctDNA guided ACT is non-inferior to SOC ACT in patients with fully resected high risk stage II and stage III resected CRC, with the potential to significantly reduce unnecessary ACT and the toxicity associated with it.

We present a plasma-only method that has high PPA and PPV with WBC genotyping for classifying non-tumor, CH variants in the cfDNA. Further investigation is underway to improve the sensitivity of annotating rare CH variants. Accurate CH identification is critical for treatment selection across targeted therapies, particularly for loss of function variants in DNA repair genes that may confer sensitivity to PARPi or ATRi therapies.

P=N/A; Trial completion date: Jul 2024 --> Jul 2026 | Trial primary completion date: Dec 2022 --> Jul 2024