TEST:

Signatera™

P3, N=700, Recruiting, IFOM ETS - The AIRC Institute of Molecular Oncology | Not yet recruiting --> Recruiting

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

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.

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, Nagoya City University

P=N/A, N=10, Terminated, Columbia University | 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)."

P=Obs | N=6,300 | GALAXY (UMIN000039205) | "Natera...announced that new data from the GALAXY arm of the ongoing CIRCULATE-Japan trial was released today at the 2024 Congress of the European Society for Medical Oncology (ESMO)....Signatera-positivity in the post-op MRD window was found to be significantly associated with worse OS compared to Signatera-negative patients (HR: 9.68, p-value < 0.01) with a 36-month OS of 71.80% vs. 96.0%, respectively....High-risk stage II and stage III-IV patients who were Signatera-positive after surgery and received ACT demonstrated superior OS (adjusted HR: 0.53, p-value = 0.05), corresponding to a 50% reduction in the risk of death when treated with ACT....Signatera-positivity after surgery was the single most significant prognostic factor associated with inferior DFS (HR 12.08, p-value <0.01) and OS (HR 9.87, p-value <0.01) in a multivariate analysis that included all clinicopathologic risk factors currently in use."

P=Obs | N=6,000 | GALAXY (UMIN000039205) | "Natera...announced it will present new data on its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, at the 2024 European Society for Medical Oncology (ESMO) Congress....The GALAXY data includes an updated analysis of more than 2,100 patients with stage I-IV CRC, reporting 36-month disease-free survival (DFS), and, for the first time, overall survival (OS). Key highlights include: Signatera-positive patients had significantly shorter OS compared to those who were Signatera-negative (hazard ratio of ~10), suggesting that Signatera-negative patients had an almost 10-fold advantage in OS. This compares favorably to all known guideline recommended biomarkers that typically have hazard ratios for overall survival in the 1-4 range. Overall survival stratified by adjuvant chemotherapy (ACT) will also be presented."

In patients with treatment-naive EBC, ctDNA is detectable after surgery. The absence of ctDNA at a single post-surgical timepoint is associated with improved DRFS, supporting the development of future trials studying de-escalation of systemic therapy.

P2; Our data indicate that the addition of ΔctDNA to baseline VIGex may refine prediction for IO.

Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.

P=N/A; Active, not recruiting --> Completed | N=1539 --> 290

Finally, ctDNA clearance predicted complete response (CR)/no evidence of disease (NED) on average 97 days (range: 0-14.7 months) ahead of imaging/biopsy. ctDNA testing in patients with DLBCL is predictive of patient outcomes and may enable personalized surveillance, intervention, and/or trial options.

"Our study demonstrates that ctDNA-based MRD may predict TNT response in LARC patients. Negative ctDNA during treatment correlates with favorable responses and may be an aid in NOM decision making."

Patients with negative ctDNA results following definitive local therapy for isolated metastatic CRC have better prognosis. Post-intervention chemotherapy in this group of patients was not associated with improved DFS. ctDNA guided omission of post-intervention chemotherapy following curative-intent local treatment of oligometastatic CRC warrants further study.

P=NA | N=NA | "Natera, Inc...announced a new study published in the Journal of Clinical Oncology highlighting the utility of its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, for surveillance in Merkel cell carcinoma (MCC)....Signatera showed a test sensitivity of approximately 95% for detecting clinically evident disease at time of enrollment. ctDNA positivity during surveillance was associated with up to 20 times higher risk of recurrence than persistently ctDNA-negative patients. At 12 months of surveillance, the recurrence-free probability was 9% among patients with a positive ctDNA result at any time, compared with 91% for patients who remained ctDNA-negative."

Conclusions : We observed a high concordance rate between primary tumor-informed vs. mLN-informed ctDNA analysis in early-stage NSCLC patients before and/or after surgery. These data support the use of alternative tissue sources for designing personalized tumor tissue-informed ctDNA assays.

Our hypothesis is that INCB099280 can be offered in selected pts as an induction and maintenance therapy instead of RC in pts who achieve a cCR.Trial design: Pts should have a predominant urotelial carcinoma (UC) histology, have a clinical stage T2-T4N0M0 MIBC, be ineligible for or refuse to receive cisplatin-based chemotherapy. The overall sample size Will be of 30 pts. Secondary endpoints will include safety (CTCAE v.5.0), event-free survival, bladder-intact overall survival (OS) and OS (EUCT number: 2024-511029-73-00).

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 II part of the study is currently open for previously untreated patient enrollment.

Post-op and post-chemo ctDNA positivity was a negative prognostic factor for DFS after 5y of follow up. Regardless of ctDNA status, DFS and OS benefit with atezo vs BSC was seen in pts with stage II-IIIA PD-L1 TC ≥1% NSCLC. Chemo-mediated ctDNA– was associated with longer DFS.

MRD positivity is significantly associated with poorer short-term OS, even among pts with recurrence, suggesting the need for escalated interventions for MRD-positive pts. In addition, ctDNA clearance is significantly correlated with superior DFS and OS, which warrants the need to evaluate ctDNA clearance as a surrogate endpoint in future clinical studies.

The personalized, tumor-informed assay can detect ctDNA pre-treatment in patients with LA SCCHN. ctDNA-positivity within 12 weeks of completing curative intent treatment was predictive of worse RFS and OS. These results may open the path to initiating treatment upon molecular recurrence in patients with LA SCCHN.

Integrating DoMore-v1-CRC, pathological stage, and ctDNA MRD enable a new paradigm in which pts with CRC will receive truly personalized adjuvant chemotherapy.

High ACN significantly correlates with ctDNA MRD as well as specific clinicopathological characteristics in CRC, suggesting a potential role in on development and aggressiveness of CRC.

The disease-free survival (DFS) benefit of adjuvant Cx was evaluated in MRD-positive and -negative groups, adjusting for age, sex, performance status, T and N status, tissue biomarkers (RAS, BRAF, and MSI), previous history of oxaliplatin for primary cancer, and postoperative complication. Among 332 CLM patients without extrahepatic disease who underwent curative surgery, 207 did not receive preoperative chemotherapy and were included in this analysis with a median follow of 22.8 months... Our data suggest that the adjuvant chemotherapy benefit in the setting of CLM applies only to MRD-positive patients. Risk stratification strategy based on MRD status can be incorporated in future clinical trials for CLM. OS data will be awaited.

The primary endpoint is distant metastasis free survival and secondary endpoints are invasive disease-free survival, relapse-free survival, overall survival, safety and quality of life. Recruitment started in December 2023 in Belgium and is planned to open in 11 more countries in 2024: Cyprus, France, Germany, Greece, Italy, Ireland, the Netherlands, Portugal, Spain, Sweden, and Switzerland.

Despite changes in the tumor mutational landscape, assay variants selected from pretreatment tumor DNA sequencing were highly conserved in serial tumor samples over time. Understanding the biology of ctDNA shedding in response to NAT may inform the use of this biomarker in predicting clinical outcomes.

Detection of plasma ctDNA using a personalized assay is prognostic of recurrence in patients with resected RCC. Herein, we describe a successful approach for its application and identify potential limitations to be addressed in future studies.

ctDNA testing in patients with bladder cancer undergoing RC was prognostic and potentially predictive. Identification of patients at high risk of recurrence may aid in patient counseling and decision-making.

Here we show a 100% 3-year DFS in patients with dMMR colon cancer treated with one dose of ipilimumab and two doses of nivolumab prior to surgery. The survival data are also supported by negative ctDNA at the MRD timepoint in all patients, while on-treatment ctDNA dynamics provide an additional monitoring instrument for future trials on organ preservation.

P=N/A; Trial completion date: Dec 2028 --> Jun 2030 | Trial primary completion date: Dec 2028 --> Jun 2030

P3 | N=700 | Not yet recruiting | Sponsor: IFOM ETS - The AIRC Institute of Molecular Oncology

P2; Trial completion date: Jun 2029 --> Sep 2029 | Initiation date: Jun 2024 --> Sep 2024 | Trial primary completion date: Jun 2026 --> Sep 2026

"Natera...announced a new gastroesophageal cancer trial, DECIPHER, that will utilize the company’s personalized and tumor-informed molecular residual disease (MRD) test, Signatera™, to guide patient selection and assess the rate of MRD clearance in patients being treated for gastroesophageal cancer."

"Natera...announced that enrollment has begun in the CIRCULATE-Japan and BESPOKE CRC trials, with both studies experiencing strong interest from centers across Japan and the U.S. The studies will measure clinical outcomes of Signatera molecular residual disease (MRD) testing in resectable Stages II-IV colorectal cancer (CRC)."

P2; Trial completion date: May 2025 --> Mar 2024 | Active, not recruiting --> Terminated; slow accrual