TEST:

RaDaR™ assay

Our data indicate that ctDNA detection after surgery can identify patients with worse prognosis, and serial ctDNA measurements may enable earlier identification of disease recurrence.

P3, N=180, Not yet recruiting, Prof. Wolfgang Janni

MRD– was maintained for most patients during adjuvant osimertinib treatment with the majority of MRD or DFS events occurring post-adjuvant osimertinib. MRD detection could potentially identify a subset of patients likely to benefit from longer adjuvant osimertinib.

Compared with either adults recruited to RaDaR or the English population, children recruited to RaDaR were more likely to be of Asian ethnicity (17.3% vs. 7.5%, P-value < 0.0001) and live in more socially deprived areas (30.3% vs. 17.3% in the most deprived Index of Multiple Deprivation (IMD) quintile, P-value < 0.0001). We observed no evidence of systematic biases in recruitment of patients into RaDaR; however, the data provide empirical evidence of negative economic and social consequences (across all ethnicities) experienced by families with children affected by rare kidney diseases.

This study represents one of the largest prospective cohorts of ctDNA assessment in patients with early stage resected NSCLC. Non-shedding patients were less likely to be male, current smokers, have PD-L1 high tumours, and were more likely to have an identifiable driver mutation. As data matures, we will be able to characterize non-shedding patients whom are at high risk of relapse and offer personalized approaches to escalation of treatment.

We show sensitive tumor-informed detection of ctDNA is possible even from 'real-world' samples of suboptimal quantity, and is prognostic in samples collected before and soon after treatment. The predictive value of ctDNA may be useful to guide (neo)adjuvant treatment. An expanded analysis will be presented.

Pts are randomly assigned (2:1) to receive treatment with BMS-986213 (Arm A: nivolumab/relatlimab) IVQ4W or monotherapy with anti-PD-1 (Arm B: nivolumab) IVQ4W for up to 12 doses. Study enrolment is ongoing. A total of 270 pts will be pre-screened for ctDNA detection with a target accrual of 54 ctDNA-positive pts, of whom 36 will be randomized to Arm A and 18 to Arm B.

The use of ctDNA detection in surgically treated patients with HNSCC has significant potential to guide treatment decisions, improve disease outcome and potentially spare patients unnecessary, partially invasive interventions during clinical follow-up. Our work demonstrates the feasibility of tumor-informed ctDNA assays for detection of MRD postoperatively and for monitoring for early detection of relapse.

Rilvegostomig (AZD2936) is a monovalent bispecific TIGIT/PD-1 antibody that has shown acceptable safety in phase I studies, currently in phase III studies...Exploratory analyses include: ctDNA detection using other assays (HPV DNA, methylated ctDNA), ctDNA detection in part E and beyond W10 in part D, quality of life assessments (FACT-ICM, EORTC-HN43), health economics and radiomics. As of February 2024, 19 patients are recruited.

Undetectable levels of ctDNA at any point during ICB treatment were strongly predictive of achieving CR, PR, or SD in patients with R/M HNSCC.

This study represents one of the largest prospective cohorts of ctDNA kinetics in patients with resected lung cancer. Of patients with at least 12 months follow up, 8/72 experienced a lung cancer recurrence with a higher rate in those with pre-operative ctDNA detected (16.7% vs 7.5%). Pre-operative ctDNA detection may help identify patients with resected stage I NSCLC that could benefit from treatment intensification, currently under study in ctDNA Lung RCT (NCT04966663).

This study demonstrates the potential of ctDNA as a dynamic biomarker for monitoring disease burden in pts with high-risk early-stage breast cancer, highlighting its remarkable sensitivity at baseline and its capability for MRD detection preceding clinical recurrence. These findings suggest the need for further research to fully understand the relationship between ctDNA dynamics during and after NACT with prediction of breast cancer outcomes. ctDNA detection rates in plasma samples across collection timepoints.

Secondary objectives include IDFS, DDFS, DRFS, BCSS and quality of life (QoL). Aims: We propose a liquid biopsy guided follow-up method, with high sensitivity and specificity for the earlier detection of distant (oligo-)metastases, to enable earlier initiation of therapy.

Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand.

Polyclonal metastasis is a common mode of metastasis in TNBC, with frequent detection of primary tumor subclones in the metastasis. NAC provides an evolutionary bottleneck, with subclones detected post NAC being the most likely to persist into the MRD and subsequent relapse. Relapsed cancer frequently had subclones not detected in the primary cancer, with approximately half of these potentially late arising, and half detectable in MRD suggesting early establishment of diversity.

RaDaR enabled sensitive ctDNA monitoring in 91% HR+/HER2- mBC pts on ET + CDK4/6i. ctDNA levels were prognostic and fell rapidly with therapy, but suppression occurred in less than one-third of pts, taking a median of 5.2 mo. Pts with negative/decreasing ctDNA may require less frequent clinical/radiographic tumor evaluations.

The RaDaR assay but not CAPP-seq may detect MRD in patients who relapse within 1 year. HPV-seq may be more sensitive than dPCR for MRD detection.

Background: The PENELOPE-B phase III trial investigated the addition of one year of palbociclib to endocrine therapy (ET), in patients with hormone receptor positive HER2 negative breast cancer with residual invasive disease after neoadjuvant chemotherapy... Detection of ctDNA following neoadjuvant chemotherapy, and surgery, is associated with a very high risk of early relapse suggesting limited efficacy of adjuvant ET. Clinical imaging and studies of experimental therapy are warranted in this patient population. Testing ctDNA after recent neoadjuvant chemotherapy in luminal-A like breast cancer has relatively low ‘sensitivity’ for predicting future relapse, in particular for later relapses, in part suggesting that response to neoadjuvant chemotherapy may reduce ctDNA detection

"NeoGenomics, Inc...announced that NeoGenomics Laboratories, Inc., a subsidiary of NeoGenomics Inc., will appeal the preliminary injunction issued by the United States District Court for the Middle District of North Carolina."

"Natera, Inc...announced that the federal District Court for the Middle District of North Carolina has issued a preliminary injunction, effective immediately, enjoining the RaDaR assay from NeoGenomics Labs, Inc."

"NeoGenomics, Inc...announced new data highlighting its RaDaR assay for minimal residual disease (MRD) will be presented at the 46th annual San Antonio Breast Cancer Symposium (SABCS)."

RaDaR detects ctDNA in most patients prior to the initiation of NAT for EBC. Changes in ctDNA levels during treatment and its presence are associated with clinical outcomes. Prospective evaluation and integration of RaDaR testing into clinical trials are warranted.

Patients with rare kidney diseases differ from the general CKD population: they are more likely to reach ESKD and half as likely to die with CKD stages 3-5, so are disproportionately represented in the RRT population. Successfully addressing unmet need in rare diseases may therefore have a disproportionate effect on RRT demand long term.

Given the comparability of eGFR decline prior to and after passing an eGFR of 45ml/min/1.73m2, slope measurements in early disease stages may be useful in estimating future eGFR loss. Comparability of eGFR slopes but differences in TA-PU suggest patients with stable rates of eGFR loss suffer increasing damage to the glomerular filtration barrier.

RaDaR is a large and robust data source allowing investigation into C3G/IC-MPGN natural history. We found heterogeneity of current treatment approaches in this cohort and rapid progression to kidney failure despite current treatments.

Outcomes in this large IgAN cohort have been published and shown to be poor with few patients expected to avoid kidney failure in their lifetime. This analysis demonstrates even worse outcomes if more socioeconomically deprived & highlights the need to develop strategies to ensure equity of access not only to early diagnosis but also to the new therapies that are showing promise in preventing kidney failure in IgAN.IMD QuintilesAge at diagnosis(median, 25th & 75th pctl)Gender (M/F)(% IMD quintile)White/ non-White (%)eGFR at diagnosis(median, 25th & 75th pctl)Time to kidney failure(median, 95% CI)1- most deprived38.9 (28.4, 51.2)67.3/32.775.2/25.838 (21, 69)7.9 (6.9, 9.3)341.0 (29.4, 51.9)69.9/30.186.2/13.839 (22, 70)10.4 (9.0, 12.6)5- least deprived41.6 (30.6, 55.0)74.3/25.788.5/11.537 (22, 68)12.4 (11.1, 13.5)

Precision medicine has become increasingly important for management of cancer patients including comprehensive genomic profiling (CGP) and molecular residual disease (MRD). Join us to learn more about NeoGenomics suite of advanced sequencing tests.NeoComprehensive™ – Solid Tumor and NeoComprehensive™ – Myeloid leverage both DNA and RNA sequencing analysis to detect multiple classes of genomic alterations that are relevant for diagnosis, therapy selection, prognosis, and clinical trials.RaDaR® is a personalized liquid biopsy test for the detection of MRD and recurrence, detecting the trace amounts of ctDNA that remain after surgery or other curative intent treatment, and early signs of relapse.

P2; Not yet recruiting --> Recruiting

"Natera, Inc...announced that it has filed a lawsuit in the North Carolina Federal District Court against NeoGenomics Labs, Inc. ('NeoGenomics') for infringement of Natera’s U.S. Patent Nos. 11,519,035 and 11,530,454 by NeoGenomics’ RaDaR molecular residual disease assay."

There was a trend for enhanced efficacy of mRNA-4157 + pembro across BRAF V600E/K WT (n=96) (HR &lsqb;95% CI]: 0.808 &lsqb;0.366–1.784]) and MUT (n=61) subpopulations (0.332 &lsqb;0.130–0.850]); however, considering ctDNA status by focusing on ctDNA-negative subpopulation increased similarity of efficacy across BRAF WT (n=68) and MUT (n=42) subgroups (0.334 &lsqb;0.121–0.923] vs 0.069 &lsqb;0.009–0.563]). Table: LBA49 ctDNA subgroup Patient criteria Molecular responders Patients with MRD at baseline that resolved during treatment (ctDNA positive at treatment initiation became ctDNA negative) OR Patients with no MRD at baseline that became ctDNA positive on treatment (MRec), and then ctDNA negative again Molecular non-responders Patients with MRD at baseline that did not resolve during treatment (ctDNA positive at treatment initiation and stayed positive) OR Patients with no MRD at baseline who showed molecular progression (MRec, ctDNA negative at treatment initiation became ctDNA positive and stayed positive) Conclusions These results suggest a potential relationship between ctDNA dynamics and treatment outcomes in pts with high-risk resectable melanoma and support further exploration in upcoming planned studies.

"NeoGenomics, Inc...announced today that the Molecular Diagnostics Services Program (MolDx) has conveyed coverage for the RaDaR assay, a personalized liquid biopsy for minimal residual disease (MRD) and recurrence detection...Following this decision, effective as of March 24, 2023, the RaDaR assay is now covered for fee-for-service Medicare patients within the United States with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer."

In patients with early stage NSCLC (small, node negative tumors), 25% have detectable ctDNA pre-operatively. Surgical resection led to ctDNA clearance in 94% of cases. Our results support ongoing testing beyond the initial MRD landmark in patients with surgically resected disease.

"NeoGenomics, Inc...announced that its RaDaR assay, a personalized liquid biopsy for minimal/molecular residual disease (MRD) and recurrence detection, has obtained its first pan-cancer commercial coverage by Blue Shield of California."

"NeoGenomics, Inc...announced new data in support of its RaDaR assay for the detection of molecular residual disease (MRD) and recurrence in patients with high-risk hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer."

"NeoGenomics, Inc...announced new data supporting its cancer tests and treatment guidance tools will be showcased in five poster presentations at the 2023 American Society of Clinical Oncology (ASCO^®) Annual Meeting taking place June 2-6 in Chicago, Illinois....Posters showcasing NeoGenomics' MRD and recurrence monitoring efforts include a Trials in Progress presentation for what is believed to be a first-in-its-kind MRD-directed interventional study in high risk, early stage HER2+ breast cancer, 'KAN-HER2 MRD' (NCT05388149)....Also being presented are findings from five studies using the RaDaR MRD assay in lung, breast, and head and neck cancers, as well as the InVisionFirst^®-Lung liquid biopsy in metastatic non-small cell lung cancer."

HPV DNA and ctDNA can be detected in LA-HNSCC before and after definitive therapy. RaDaR but not CAPP-seq may detect MRD in pts who relapse within 1 year after RT/CRT with a significant lead time. HPV-seq may be more sensitive than dPCR to detect HPV DNA in MRD.

MRD detection by plasma ctDNA assay at the start of adjuvant melanoma treatment is uncommon in mRNA4157-p201 but is associated with shorter RFS. Treatment with the combination of mRNA-4157/V940 and pembrolizumab was associated with prolonged RFS compared to pembrolizumab monotherapy in patients with high-risk resectable melanoma, irrespective of MRD status Additional analyses including assessment of longitudinal ctDNA patterns are ongoing. The association between MRD and mRNA-4157/V940 treatment effect will be further explored in upcoming planned studies.

ctDNA detection by RaDaR assays predicted recurrence in two independent cohorts, confirming the potential to identify patients for adjuvant treatment. In stage I patients with positive ctDNA, adjuvant treatment could be offered with confidence due to high specificity of 99% and PPV of 91%. In stage II-III patients, the primary cancer recurred in a quarter of patients with no ctDNA detected post-treatment (NPV 74%).

Detection of ctDNA in early-stage breast cancer is challenging. Our data suggests association of ctDNA detection with some pathological and clinical variables. Independent validation is needed.

Background: The PENELOPE-B phase III trial investigated the addition of one year of palbociclib to endocrine therapy (ET), in patients with hormone receptor positive HER2 negative breast cancer with residual invasive disease after neoadjuvant chemotherapy... Detection of ctDNA following neoadjuvant chemotherapy, and surgery, is associated with a very high risk of early relapse suggesting limited efficacy of adjuvant ET. Clinical imaging and studies of experimental therapy are warranted in this patient population. Testing ctDNA after recent neoadjuvant chemotherapy in luminal-A like breast cancer has relatively low ‘sensitivity’ for predicting future relapse, in particular for later relapses, in part suggesting that response to neoadjuvant chemotherapy may reduce ctDNA detection.

KAN-HER2 represents the first reported MRD-directed interception trial for HER2-positive breast cancer. Clinical trial information: NCT05388149.

"NeoGenomics, Inc...announced today that the company and its collaborators will present a total of nine abstracts at the American Association for Cancer Research (AACR) Annual Meeting 2023 taking place April 14-19, 2023 in Orlando, Florida...NeoGenomics, alongside collaborators, will present new data demonstrating the broad portfolio of services and available validated assays focused on tumor biology, including the use of RaDaR, a personalized, highly-sensitive liquid biopsy sequencing test for the detection of minimal residual disease (MRD) and recurrence."