TEST:

Signatera™

ctDNA monitoring is feasible for patients with high-risk cutaneous melanoma. Our findings suggest that detectable ctDNA post-operatively may be associated with worse outcomes. Elevations during surveillance may predict subsequent clinical recurrence; however, the role of ctDNA in adjuvant therapy decision-making and surveillance is not yet ready for broad application.

P1, N=16, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

P2, N=44, Recruiting, Diwakar Davar | Not yet recruiting --> Recruiting | Trial completion date: Nov 2029 --> Mar 2030 | Trial primary completion date: Nov 2026 --> Mar 2028

P=N/A, N=28, Active, not recruiting, University of Utah | Trial primary completion date: Feb 2025 --> Jun 2025

P=N/A, N=350, Not yet recruiting, National Cancer Center, Japan

P=N/A, N=50, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P2, N=100, Recruiting, University of Alabama at Birmingham | Trial primary completion date: Dec 2024 --> Jul 2025

"Natera... today announced that the first set of abstracts have been released from several studies that will be shared at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium (ASCO GI) taking place Jan. 23 – 25, 2025 in San Francisco, CA."

P2, N=20, Not yet recruiting, Imperial College London | Initiation date: Nov 2024 --> Feb 2025

"Natera, Inc...will provide an update to the investment community, today, at the 43rd annual J.P. Morgan Healthcare Conference. In addition to its previously announced preliminary financial results for the fourth quarter and year ended Dec. 31, 2024, the Company will also present details on its innovation roadmap for oncology."

P2, N=70, Recruiting, Criterium, Inc. | N=100 --> 70 | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2027

P=N/A, P3; Two cycles of neoadjuvant osimertinib did not meet its primary endpoint of ORR. Neoadjuvant osimertinib is a feasible approach with a manageable safety profile in resectable EGFR-mutant NSCLC.

Collectively, we show that serial ctDNA monitoring provides prognostic information for patients undergoing treatment or surveillance, and our findings demonstrate high concordance between ctDNA status/dynamics and subsequent clinical outcomes.

Within the subgroup of patients with EGC and favorable pathologic responses (TRG 0-1) after NAT, the presence of postoperative ctDNA identified patients with elevated recurrence risk.

When ctDNA status is used alongside the NAR score in the post-NAT setting, patients who were ctDNA-positive with an intermediate or high NAR score showed significantly worse DFS (HR: 47.5, p < 0.001) compared to ctDNA-negative patients with either a low or intermediate/high NAR score (HR: 9.8, p = 0.0301). Post-NAT ctDNA status, whether used alone or in combination with the NAR score, may predict NAT response, and improve risk stratification.

"Natera, Inc...today announced that it will present new Signatera™ data at the San Antonio Breast Cancer Symposium (SABCS), taking place Dec. 10-13 in San Antonio, TX...Four abstracts to be presented at SABCS evaluated patient reported outcomes when testing for circulating tumor DNA (ctDNA). The data indicates that ctDNA testing can provide valuable information for treatment planning while not causing increased anxiety in patients."

Detectable ctDNA status in the pre-RPLND status was associated with viable GCT on histology while having normal STM. Undetectable pre-RPLND ctDNA was associated with either no tumor or teratoma on histology. Detectable ctDNA status at the MRD window was associated with disease progression in all patients while only 25% had elevated STM.

IMvigor011 (NCT04660344) is a randomized Phase III study assessing atezolizumab versus placebo in patients with high-risk MIBC who are ctDNA+ post-cystectomy based on a personalized (tumor-informed) assay (NateraSignatera TM )... This exploratory analysis of the phase III IMvigor011 surveillance cohort demonstrated that serial ctDNA testing may have greater clinical utility as a risk stratification tool than landmark ctDNA testing in patients with high-risk MIBC post-cystectomy. Furthermore, the data lend increasing confidence that patients with high-risk MIBC who have persistent ctDNA– status after cystectomy may not require adjuvant treatment. A follow-up analysis will be completed as part of the primary IMvigor011 analysis.

"Natera, Inc...today announced the completion of a study using Signatera from the CALGB (Alliance)/SWOG 80702 randomized, phase III clinical trial. CALGB (Alliance)/SWOG 80702 evaluated the benefit of adding celecoxib to FOLFOX in postoperative treatment of stage III colorectal cancer (CRC) in a biomarker unselected population."

P3; Not yet recruiting --> Recruiting

P=N/A; N=50; Recruiting; Sponsor:Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

Our study suggests that ctDNA can complement radiographic imaging for detection of STS recurrence and for monitoring response to therapy. Incorporating ctDNA testing to routine sarcoma care may provide additional data points to optimize frequency of imaging and enhance quality of care. Additional research is ongoing to improve sensitivity of ctDNA detection in the adjuvant setting.

Patient was on pazopanib after initial treatment with surgery and chemotherapy, and there was no tumor evidence... Given each sarcoma patient's unique initial disease, remission, and recurrence, the use of ctDNA testing demonstrated promising use compared to traditional imaging studies in the sarcoma patients reported, appearing to indicate evidence of disease recurrence and progression. The patient cases analyzed here hold promise for ctDNA as an additional tool to traditional surveillance methods, given the assay's ability to correlate precisely to disease recurrence or progression. In three of four patients, positive ctDNA results were obtained before imaging studies and revealed signs of recurrence.

Five patients received two lines of immunotherapy (pembrolizumab followed by ipilimumab/nivolumab [n = 4] and anti-PD-1 clinical trial drug followed by ipilimumab/nivolumab [n = 1]). Other systemic therapies used concurrently with immunotherapy were cabozantinib (n = 6), temozolomide (n = 2), pazopanib (n = 2), palbociclib (n = 2), gemcitabine (n = 1), ivosidenib (n = 1), and carboplatin/paclitaxel (n = 1)... Decline in ctDNA demonstrates correlation with radiographic response to immunotherapy and improved survival and could be a potential early biomarker of therapeutic efficacy in advanced soft tissue sarcomas.

Taken together, the data shows that (1) lurbinectedin combined with ipilimumab and nivolumab is a safe regimen with a MTD of 3.2 mg/m2 for lurbinectedin and (2) there were no serious treatment related adverse events reported. The Phase 2 part of the study is currently open for previously untreated patient enrollment.

In 5 patients with PTCL, ctDNA negativity showed 100% concordance with negative PET-CT results. Our results, albeit with small numbers, suggest that ctDNA is strongly associated with clinical outcomes in patients with PTCL; ctDNA may serve as a useful tool to monitor and prognosticate patients with PTCL when validated in a large cohort of patients.

The scientific promise of ctDNA testing is clear; however, considerable challenges remain before payers reimburse NGS-based ctDNA tests required for proactive detection. Ultimately, payers will need to be convinced that ctDNA testing provides economic and therapeutic value to patients and healthcare systems.

The ZEST study was terminated early because of infeasibility of completing enrollment due to a low rate of ctDNA+ and a high rate of metastatic disease at the time of ctDNA+. Although ctDNA testing began any time after EODT, ctDNA+ occurred most frequently on the first test and ≤6 months from EODT. Pts, predominantly those with TNBC, had a high rate of radiographic recurrence at time of ctDNA+, consistent with early recurrence typical of TNBC.

Conclusions In this study, most pts with eBC valued the information they received through the personalized, tumor-informed ctDNA test and would continue ctDNA testing. Monitoring ctDNA led to minimal to no change in average anxiety scores even after a positive result.

This interim analysis suggests that ctDNA surveillance may not adversely affect patient anxiety. However, further follow up and future randomized trials are needed.

This pilot study shows the feasibility of testing ctDNA in clinical practice and explores its association with symptoms and outcomes. Further analysis with a patient population followed for a longer period will be required to understand the impact of ctDNA testing on the well-being of patients with breast cancer.

To our knowledge, this is the first analysis incorporating comprehensive WES data with tumor-informed ctDNA analysis to evaluate the impact of targetable genomic alterations on ctDNA detection and DRFS in early-stage HR+ breast cancer. Overall, 44% of patients with ctDNA+ had at least one targetable genomic alteration. Among patients with early ctDNA positivity, those with PIK3CA mutated tumors tended to have worse early DRFS than those with PIK3CA WT tumors.

This study enrolled older pts, in whom "right-sizing" therapies for ER+ BC is critical. ctDNA results were highly associated with disease outcome, and persistent ctDNA positivity conferred significant risk for progression. ctDNA monitoring may help identify those pts with indolent disease who may be safely followed on pET and those who may be at risk for AI resistance.

No dose-limiting toxicities (DLTs) were observed; however, one patient experienced Grade 2 cytokine release syndrome (CRS) (table 2), managed with tocilizumab...Ongoing analyses include phenotyping of pre- and post-infusion CBNK cells, donor NK cells, and other immune cell types. Conclusions The combination of cetuximab with pre-A+E CBNK cells is safe and demonstrates promising efficacy for treating MRD in CRC.View this table:View inline View popup Download powerpoint Abstract 1457 Table 1 Patient characteristicsView this table:View inline View popup Download powerpoint Abstract 1457 Table 2 Safety dataView this table:View inline View popup Download powerpoint Abstract 1457 Table 3 ctDNA clearance: ad interim report

P=N/A; N=50; Enrolling by invitation; Sponsor:Nagoya City University

P=N/A; N=37 --> 10 | Recruiting --> Terminated; Low accrual

In a pt subset from monarchE enriched for IDFS events, ctDNA detection was relatively infrequent (<20%); however, its detection at any time during the 24 months of study therapy was adversely prognostic. As compared to pts who had remaining ctDNA positive (+), pts who had clearance of ctDNA on therapy had lower risk of IDFS events, but the event risk still remained clinically meaningful in these pts.

This cohort included Stages I (N=38), II (N=1), III (N=11), and IV (N=10) patients. Median clinical follow-up was 10.2 (0.9-37.7) months and median number of blood draws per patient was 4 (1-17). ctDNA detection rates following surgery and upfront therapy were 32% (7/22) and 33% (9/27), respectively.

P2; N=20; Not yet recruiting; Sponsor:Imperial College London

P2; Recruiting --> Active, not recruiting

"Natera, Inc...announced the simultaneous publication of three peer-reviewed papers, crossing a milestone of more than 85 peer-reviewed publications on Signatera...CRC Data from GALAXY ( Nature Medicine & ESMO Poster)...CRC Data from GALAXY ( Annals of Oncology & ESMO Poster)."

Methods Pts with cT2-4N0M0 MIBC with pure/predominant urothelial carcinoma histology, who were ineligible for or refused cisplatin-based chemotherapy, received 4 cycles of SG 10 mg/kg (days 1,8 q3w) followed by RC. Conclusions The observed ypT0N0-x responses after neoadjuvant SG demonstrate promising activity in MIBC, unveiling a potential to avoid RC. Reduced dose of SG was feasible, and the data support the ongoing SURE-01 study in MIBC.