TEST:

Idylla™ EGFR Mutation Test

The Idylla™ system is a rapid and effective method that enables sensitive and reliable detection of EGFR mutations in FFPE samples of NSCLC patients, with minimal molecular expertise or infrastructure.

The Idylla EGFR mutation assay is highly concordant with commercially available NGS tests. It offers several advantages, including reduced TAT, minimal hands-on time, and lower sample input requirements.

However, NGS had a 12-day longer TAT compared to EGFR PCR. Gene fusion-panel PCR and NGS identified an additional 11.6% of patients harboring actionable alterations who may benefit from FDA-approved targeted therapies.

The high EGFR-positivity rate among ultra-stat tested patients indicates effective identification of probable EGFR-positive cases by clinicians, with race being the most significant predictor of EGFR mutation. These findings will support the development of decision aids for selection of EGFR testing modality.

Additionally, three of the patients, who had measurable tumors, showed partial responses to afatinib and osimertinib. The L858R mutation associated with L858R-K860I and L858R-L861F doublet mutations could be detected using Idylla but not cobas EGFR tests. Using next-generation sequencing analysis should be considered after initial negative reports from the cobas test, because patients with L858R doublet mutations may benefit from EGFR-TKIs.

The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.

Clinically urgent cases with adequate cellularity, can first perform Idylla to detect critical markers, then perform NGS for a comprehensive mutation analysis. Besides, with limited molecular expertise or infrastructure, the Idylla has the potential to extend EGFR testing to more pathology laboratories in primary hospitals.

P=N/A; Phase classification: P3 --> P=N/A | N=130 --> 0 | Trial completion date: Jun 2024 --> Dec 2023 | Not yet recruiting --> Withdrawn

The Idylla EGFR test performance is comparable to reference methods and with a shorter TAT. Adding a concurrent plasma Idylla test to tissue NGS testing increases the detection rate of EGFR mutations in NSCLC.

The Idylla Rapid IDH1/2 Mutation Assay had 92% concordance with NGS for FFPE sections. Compared with Idylla EGFR and KRAS assays (previously published) both control and target Cqs were considerably higher using the same number of sections or amount of DNA. A large DNA input requires stewardship for effective tissue utilization for molecular testing, especially in glioma biopsy samples, which may be limited.

"Biocartis Group NV...announces that four study abstracts on Idylla™ have been selected for poster presentations at the international ESMO (European Society of Molecular Oncology) congress, taking place between 20-24 October 2023 in Madrid (Spain). The studies show excellent data for the Idylla™ GeneFusion Assay and Idylla™ EGFR Mutation Assay....The first study prospectively tested lung cancer samples on the Idylla™ Platform as part of routine2 lung profiling locally and from over 60 UK hospitals....The second abstract presents the results of a multicenter study that was conducted in a routine clinical2 setting involving 12 clinical centers across Europe....The third abstract presents the results of the ORIGEN study, a multicenter study on the prevalence of EGFR gene mutations in patients with early-stage resectable non-small cell lung cancer in Spain (in collaboration with AstraZeneca Spain)."

P3; N=130; Not yet recruiting; Sponsor:Biocartis NV

Table: 1278P Common EGFR mutations according to tumor stage Conclusions In this series of pts operated on for NSCLC, frequency of EGFR mutation was 15%, the most frequent being exon 19 deletions and the L858R mutation, in line with data reported in Spain in advanced NSCLC. These results reinforce the importance of performing EGFRm testing in early-stage NSCLC to identify pt candidates to adjuvant osimertinib.

The Idylla™ EGFR fully automatic PCR system directly detects EGFR mutations in fresh tissues. The operation is simple, the detection time is short, and the accuracy is high. The detection time is reduced to 1/4-1/3 of the original time while meeting clinical standards for detecting the gene status of patients, thus saving crucial time for individualized and accurate treatment of patients. The method has promising clinical application prospects.

The Idylla EGFR testing is an accurate and simple tool useful for the early screening of EGFR mutations. The Idylla GeneFusion is a potential screening panel with short turnaround time using a minimal amount of tissue and might be considered as a relevant complementary testing to IHC in diagnostic molecular laboratories.

We demonstrated the accuracy and potential clinical utility of the Idylla EGFR Mutation Test as a molecular screening platform in terms of turnaround time and molecular testing cost if applied to a cohort with a high EGFR mutation incidence (>17.9%).

Combining tissue and liquid NGS profiling provides the best treatment selection outcomes for patients with metastatic NSCLC. Our study highlighted that a quarter of NSCLC patients in Singapore would be identified for eligible targeted treatments from adopting a nationwide NGS testing approach, ideally tissue and liquid combined, to improve cancer services.

Image-based molecular detection can serve as an accurate and fast detection method to be used in the clinical setting for monitoring and prioritizing current pathology workflow. Specifically, it can detect a major fraction of the non-targetable patients and optimize their diagnostic flow.

When compared to ARMS-PCR, the Idylla™ system demonstrated high accuracy with an overall agreement of 97.1% (34/35), a sensitivity of 95.2% (20/21) (95% CI, 76.2% - 99.9%), and an estimated specificity of 100% (12/12) (95% CI, 76.8% - 100%) for 35 prospective samples. This Idylla system provides a rapid, accurate and simple approach for screening EGFR mutations, which can guide Tyrosine Kinase Inhibitors (TKI) treatment for NSCLC patients in a timely manner.

P=N/A | N=55 | Completed | Sponsor: Royal Cornwall Hospitals Trust | Recruiting ➔ Completed | N=200 ➔ 55

The Idylla™ EGFR Mutation Test performed well versus local methods and had shorter analytical turnaround time. The Idylla™ EGFR Mutation Test can thus support application of personalized medicine in NSCLC.

"Biocartis Group NV...announces the recent publication of a new, large prospective study1 demonstrating that the Idylla™ EGFR Mutation Test (CE-IVD2) leads to the significant reduction of the time-to-treatment by 48% or on average 16.8 days faster than NGS testing for EGFR positive patients. This shows Idylla™’s potential to improve strategic treatment decisions within a multidisciplinary team for patients with advanced non-small cell lung cancer (NSCLC)....The study showed a concordance of 98.7% between the Idylla™ EGFR Mutation Test and the NGS panel. The lab turnaround time was faster for the Idylla™ EGFR Mutation Test by an average of 12.4 days. In the EGFR positive cohort, the Idylla™ EGFR Mutation Test led to a 48% reduction and on average 16.8 days faster turnaround time."

"Biocartis Group NV...announces the publication of nine performance study abstracts of its fully automated molecular diagnostics Idylla™ platform and assays at the annual meeting of the ‘Association for Molecular Pathology’ (AMP), a leading molecular diagnostics conference, taking place between 1-5 November in Phoenix, Arizona (US). The studies were performed by a variety of US laboratories and research institutes."

Using the Idylla EGFR test as part of the molecular testing repertoire in advanced-stage NSCLC patients could significantly reduce TTT.

"The 23 common mutations detected in the BRAF and NRAS genes using this assay have significant impact on therapeutic selection. Somatic variants in the BRAF gene have been found in 37%-50% of all malignant melanomas, whereas somatic variants in the NRAS gene are found in 13%-25% of all melanomas. The Biocartis Idylla system offers a simple and rapid method to obtain somatic mutation information in these two genes that are of clinical importance."

Our validation study affirms that the Idylla EGFR mutation assay enables streamline, rapid, accurate and reproducible EGFR genotyping of FFPE samples with tumor cellularity above 10%.

The Idylla EGFR assay demonstrated high specificity and sensitivity for identifying exon 18 and 21 SNVs, and exon 19 deletions. However, the platform has not detected any of the exon 20 insertions seen in our cohort, leading to erroneous results and potentially compromising patient care if this is the only platform used. These insertion mutations are not included in the Idylla EGFR assay design, which is a significant limitation of this assay.

No abstract available

No abstract available

Idylla EGFR on extracted DNA is feasible and enables tumour material to be saved compared with tissue section use. It is not necessary to replace the analytical thresholds of the Biocartis algorithm. Due to both the limits of the mutational repertoire and the high increase of targetable genes in NSCLC, the use of Idylla EGFR should be restricted to clinical emergency situations accompanied by NGS.

"Biocartis Group NV...announced that it has entered into an agreement with AstraZeneca...aimed at the development and applicable pre-market notification or approval with the US FDA of a novel companion diagnostic1 (CDx) test on Biocartis’ molecular rapid and easy-to-use diagnostics Idylla™ platform, for use with Tagrisso® (osimertinib)....Under the terms of the agreement, Biocartis and AstraZeneca will co-lead the development and applicable pre-market notification or approval of the Idylla™ EGFR CDx Assay intended to aid in identifying patients with non-small cell lung cancer (NSCLC) who may respond to treatment with Tagrisso®. In addition to FFPE2 tissue, Biocartis will seek to validate the use of less invasive cytology samples such as fine needle aspirates3 for use with the Idylla™ EGFR CDx Assay, to expand patient access to testing."

The Idylla system provides a rapid and accurate ability to differentiate result of ARMS-PCR of EGFR in gray area and identify more rare mutation variants which may decrease the repeat testing or validation. But the ability of NGS to find more actionable variants is still important.

No abstract available

P3 | N=380 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting --> Recruiting

The overall agreement between results obtained with the Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR was 100% Our results showed that EGFR mutation is a rare mutation type in a consecutive series of de novo SCLC. Furthermore, the performance of Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR on archived paraffin sections of limited quantities is available with the high agreement of results.

This audit identified good compliance with target of 10 days for specimens requiring molecular testing. It helped to highlight key issues in regard to testing turnaround time and act as a local catalyst for optimising molecular testing in lung cancer specimens. PCR testing for EGFR mutations using the Idylla platform is judged a fast and reliable way to obtain reliable results, which avoids the delay and logistical overhead of sending material offsite.

Detection of EGFRex20ins is necessary to identify patients suitable for amivantamab and mobocertinib. Commonly used PCR assays may fail to detect EGFRex20ins in 50% of patients potentially suitable for approved targeted therapies. Identification of EGFRex20ins can be improved with NGS-based testing. Our data confirm that NGS is superior to PCR-based assays and is the preferred NSCLC genotyping technology.

No abstract available

"Biocartis Group NV...announces the publication of a large new study comparing the difference in turnaround time between in-house automated rapid PCR3-based EGFR analysis and Next-Generation Sequencing (NGS) by an external laboratory, with a focus on patient health outcome. The study concluded that a dual PCR and NGS testing strategy for stage IV non-squamous, non-small cell lung cancer (NSCLC) patients has the potential to improve care and survival outcomes by providing access to the right test at the right time...In the study, 102 test results for lung adenocarcinoma patients were compared using both NGS and Idylla™ EGFR Mutation Test (CE-IVD)."

We discuss issues around integrating rapid PCR testing alongside NGS in multidisciplinary care pathways and strategies for mitigating against foreseeable difficulties. Dual testing for stage IV non-squamous, NSCLC patients has the potential to improve care and survival outcomes by providing access to the right test at the right time.

In this article, we review the data about the fast and fully automated real-time PCR platform Idylla™ (Biocartis, Mechelen, Belgium) permitting the mutational analyses of BRAF, KRAS, NRAS, EGFR and microsatellite instability notably in melanoma, non-small-cell lung cancer and colorectal cancer samples. Future applications as well as the implementation of Idylla™ in the workflow of pathology and/or molecular biology laboratories are also discussed.

Subsequently, based on the Idylla method, the timeframe from tumor sampling to the initiation of EGFR-TKI was 7.7 ± 1.2 wd (11.4 ± 3.1 cd), while it was 20.3 ± 6.7 wd (27.2 ± 8.3 cd) with the NGS method (p < 0.001). We thus demonstrated here that the Idylla system contributes to improving the therapeutic care of patients with NSCLC by the early screening of EGFR mutations.