TEST:

InVisionFirst®-Lung

Conclusions NGS-ctDNA provided clinically informative results for 26% of pts with advanced lung SCC, including 6% for whom targeted therapies are available in routine practice or clinical trials (4% ESMO ESCAT tier I and 2% ESMO ESCAT tier IIB). These results suggest that molecular profiling, including plasma NGS testing, should be considered in this population.

P3; Active, not recruiting --> Completed

Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC accelerates time to treatment and yields more actionable alterations. A plasma-first approach increases access to precision medicine with the potential for improved patient outcomes.

KRAS is a complex genetic mutation associated with heterogeneity in PD-L1 expression and co-alterations, which could serve as biomarkers for differential outcomes. STK11 co-mutation appears to be a poor prognostic biomarker in this context.

The iDx-lung study will evaluate biomarkers and build a prediction model for the early detection of lung cancer to improve current LDCT screening protocols. The team of academic and industrial partners have successfully completed the set-up phase of this large-scale translational study. Recruitment, sample collection and analysis is underway.

Early LB significantly reduces the time to contributive molecular analysis and the time to initiation of appropriate 1st line therapy in pts eligible for systemic treatment, especially for pts with actionable alterations indicating targeted 1st line therapy. Clinical trial information: NCT03721120.

In patients with aNSCLC, mVAF depends on disease burden, on the molecular characteristics of the disease and on the presence and extent of liver disease. LDH levels above ULN predict the presence of ctDNA and percentage of mVAF.

P3; Recruiting --> Active, not recruiting | Trial completion date: Oct 2022 --> Aug 2023 | Trial primary completion date: Oct 2022 --> Aug 2023

In BRAF V600E -mutant NSCLC, combination therapy with dabrafenib and trametinib demonstrated robust activity, but its resistance mechanisms are poorly known. Conclusion Single CTC profiling reveals for the first-time a wide spectrum of off-target alterations in multiple oncogenic pathways from patients with BRAF -mutant NSCLC. Single CTC sequencing analysis may provide important complementary information to bulk tumor samples to assess heterogeneous resistance mechanisms and to guide precision medicine in BRAF V600E NSCLC.

In this cohort, 21% of unselected patients with advanced NSCLC had clinically actionable alterations used to guide TT in routine practice, including the cases with insufficient tissue for molecular testing. This rose to 50% when considering clinically informative GAs from tier2, where investigational targeted therapies may be considered.

"NeoGenomics, Inc...announced that its liquid biopsy focused subsidiary Inivata Limited ('Inivata') together with collaborators will present new data on its RaDaR® assay for the detection of minimal residual disease (MRD) and recurrence at the American Society of Clinical Oncology (ASCO) Annual Meeting, taking place on 3-7 June 2022. New data on the Company's InVisionFirst®-Lung liquid biopsy test will also be presented."

Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC leads to faster molecular results and shortens time to treatment compared to tissue testing alone. Supplementing the current standard of tissue molecular testing with a plasma-first approach during the diagnostic work up of patients with suspected advanced lung cancer may increase access to precision medicine and improve patient outcomes.

"NeoGenomics, Inc...announced today that they are partnering with Eli Lilly and Company on a sponsored testing program for eligible patients with metastatic non-small cell lung cancer (NSCLC) at no cost...The Lilly Lung Cancer Sponsored Testing Program will utilize the NeoTYPE® DNA and RNA Assay to provide eligible metastatic NSCLC patients with enhanced access to a targeted genomic test offering that can help physicians and patients make informed treatment decisions. For cases where results are not attainable due to low tissue input or when an invasive biopsy is medically contraindicated, eligible patients are able to instead use InVisionFirst®-Lung Liquid Biopsy at no cost."

Progression free survival was longer in patients who cleared ctDNA compared to those who did not (median 567 vs 74 d, p = 0.01). Although it is feasible to use ctDNA testing on a limited gene panel to identify patients with LA-NSCLC who are at high risk for disease recurrence following CRT, further studies will be necessary to optimize these assays before they can be used to inform clinical care in patients with lung cancer.

Median time from referral to treatment initiation was 31 days (range 16-41) if an actionable alteration was identified in plasma versus 35 days if none was identified (range 20-58).Conclusion While liquid biopsy in the initial diagnostic workup of advanced NSCLC patients may accelerate profiling Result s and treatment initiation, comprehensive NGS assays with faster TAT are needed. An expansion study (N=150) is ongoing with a comprehensive DNA-based assay with faster TAT (SNV, indels, fusions, CNV; InVisionFirst, Inivata).

P=N/A; ctDNA levels increase in the hours to days after starting treatment. ctDNA testing in the acute post-treatment phase can yield results that were not evident in pre-treatment testing. Application of this principle could improve ctDNA utility as an alternate to tissue-based testing and improve sensitivity for the detection of treatment-resistant clones.(NCT03986463).

"Conclusion The iDx-Lung academic and industrial partners have successfully completed the set-up phase of this large-scale translational study and patient recruitment and sample collection is underway. Impact statement Biomarkers will be evaluated as markers for early detection of lung cancer to improve current screening programs."

Real-time ctDNA is feasible and clinically informative in unselected pts with newly diagnosed advanced NSCLC. Preliminary data showed that LB could support the treatment selection in 68% of pts. This study is still ongoing; final data and outcomes based on ctDNA will be presented at ESMO Congress.

In samples from EGFRm ex19/21 pts treated with 1st/2nd generation (gen.) TKI (n=51), the T790M mutation was detected in 27%; in those from pts treated with osimertinib (n=15), the C797S rate was 13%. In ALKr pts treated with crizotinib (n=17), ≥1 ALK resistance mutations were found in 12% (1 G1269A+F1174L, 1 G1202R), after 2nd gen. (n=16) in 31% (3 G1202R, 1 D1203N+F1174C, 1 T1151R) and after lorlatinib (n=16) in 13% (2 G1202R)... ctDNA is feasible in pts with NSCLC harbouring EGFRm, ALKr, BRAFV600Em for detecting driver and resistance GAs at PD, providing clinical informative for treatment selection at TKI failure in 22% of cases. Outcomes of the following therapies based on ctDNA will be presented at the congress.

Single CTC profiling reveals a wide spectrum of therapeutic resistance mutations not detected by other analyses in pts with BRAFV600E-mutant NSCLC at failure to dabrafenib + trametinib. Integration of single CTC sequencing to tumor and cfDNA analysis, provides important perspectives to assess heterogeneous resistance mechanisms and to guide precision medicine in BRAFV600E- NSCLC.

Conclusion Our results demonstrate that it is feasible to employ ctDNA testing to identify LANSCLC patients who are at high risk for disease recurrence following CRT. This finding requires validation in future studies.

Next-generation, targeted, amplicon-based sequencing for liquid biopsy specimen profiling provides clinically relevant detection of ALK/ROS1 fusions in TKI-naïve patients and allows for the identification of resistance mutations in patients treated with TKIs. Liquid biopsy specimens from patients treated with TKIs may affect clinical outcomes and capture heterogeneity of TKI resistance, supporting their role in selecting sequential therapy.

"ctDNA positivity at the first-radiographic evaluation under treatment, as well as BRAF-mutant ctDNA positivity at PD were associated with poor survival. Potential drivers of resistance to either BRAF-TT monotherapy or BRAF/MEK combination were identified in 46% patients and included activating mutations in effectors of the MAPK and PI3K pathways, as well as alterations in U2AF1, IDH1 and CTNNB1 ctDNA sequencing is clinically relevant for the detection of BRAF-activating mutations and the identification of alterations potentially related to resistance to BRAF-TT in BRAF-mutant NSCLC."

"Acquired T790M at TKI relapse was detected in 73% (46/63) of patients, and all prospective patients (34/46) initiated osimertinib treatment based on ctDNA results...ctDNA molecular profiling is an accurate and reliable tool for the detection of clinically relevant molecular alterations in advanced NSCLC patients. Clinical outcomes with targeted therapies endorse the use of liquid biopsy by amplicon-based NGS ctDNA analysis in first line and relapse testing for advanced NSCLC patients."