BRAF (B-raf proto-oncogene)

P1/2, N=94, Recruiting, Deciphera Pharmaceuticals, LLC | Trial completion date: Jun 2027 --> Mar 2029

P1, N=124, Recruiting, Pfizer | Trial completion date: Sep 2028 --> Aug 2029

P1, N=122, Terminated, Novartis Pharmaceuticals | Trial completion date: Jan 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Sep 2024; The decision of early termination was made due to business reasons, and was not based on any safety concerns for any of the treatment combinations.

P1, N=46, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2024 --> Nov 2025

The Agena iPlex HS Lung Panel on the MassARRAY System is highly tolerant of poor quantity and quality DNA, recovering and delivering accurate results on samples that would otherwise fail NGS-based analysis.

Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.

SMAD4 p.G365S (c.1093G >A) is a novel inactivating missense mutation. Although this patient presented with aggressive disease, the clinical significance of this SMAD4 mutation is still uncertain. Additional meta-analytic studies are needed to determine the significance of SMAD4 alteration in patients with malignant melanoma.

The AVENIO CGP assay is an end-to-end platform for tumor genomic profiling, with proven high analytical sensitivity and specificity. Its superb performance makes it well suited for translational research, providing deep genomic analyses to accelerate cancer research.

The detection of BRAF fusions and their many partners was enabled by the Afirma XA exome-enriched RNASeq panel. Although BRAF fusions occurred in only 0.2% of thyroid nodules, they were GSC-Suspicious and lacked typical BRAF/RAS mutations. Interestingly, expression signatures associated with malignancy varied by fusion partner.

We demonstrated the feasibility of obtaining actionable information within a clinically meaningful turnaround time using a robust NGS solution. For samples with sufficient tumour content and DNA for testing (>90% of samples), Find It had an approximately 99% success rate. Actionable information provided by the panel could impact clinical management for 66% of advanced-stage cancer patients.

AFP, the targeted, breakpoint/fusion partner agnostic panel, outperformed 3 other established panels using real-world, fusion-driven thyroid cancers by an average detection frequency of 39%. Such findings demonstrate the importance in sequencing panel selection for fusion-driven thyroid cancer detection, and the potential downstream consequences for diagnostic utility and therapeutic intervention.

Given the importance of timely, comprehensive molecular test results to inform appropriate treatment decisions in NSCLC and CRC, these results suggest that the rapid in-house GeneXus NGS system can reduce TAT with comparable failure rates and alteration detection rates compared to other testing methods. Further studies evaluating the impact of the rapid OPA compared to other methods on patient care, as well as the economics of different molecular tests, are ongoing.

It is feasible to yield actionable molecular testing results from cytology specimens within 2 to 3 hours of the patient's diagnostic procedure, and aspirate smears can be triaged for this use at the time of the rapid on-site evaluation. Targetable genetic alterations can be detected from destained cytology aspirate smear slides and unstained FFPE cell blocks with high accuracy, precision, and analytical sensitivity and specificity. The cost of each cartridge ranges from $127 to $462 and is covered by the average national reimbursement schemes.

OS+ is a reliable test to identify clinically relevant genomic alterations, cnLOH, and several hotspot mutations in pediatric FFPE solid tumor specimens. WGS/WES significantly increases the yield of actionable somatic mutations and cancer-predisposing germline variants. The cost, turnaround time, and tumor percentage in the specimen make OS+ followed by WES principal tests for pediatric solid tumor analysis at our institution.

IDH1/2 mutations are identified in a small subset of NSCLCs. Our findings suggest that >25% of these mutations are hematopoietic in origin with important implications for diagnosis and management of these patients. Among those with mutations arising from the lung neoplasm, IDH1/2 mutations were primarily seen in conjunction with another driver and were subclonal in nature, suggesting patterns of clonal heterogeneity and evolution.

The assay shows good performance in detecting hotspot SNVs and small indels in ctDNA, and is suitable for clinical use. The limitation of bioinformatics pipelines in variant calling should be noted, and consideration can be given to run multiple pipelines in parallel to avoid missing out variants.

P2, N=38, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

P2, N=101, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P4, N=20, Recruiting, yangjianjun | Initiation date: Jan 2024 --> Sep 2024

P1, N=50, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

P2, N=62, Suspended, Oslo University Hospital | Recruiting --> Suspended | Trial primary completion date: Mar 2024 --> Dec 2024

P1/2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P=N/A, N=12, Not yet recruiting, Huashan Hospital, Fudan University; Huashan Hospital, Fudan University | N=20 --> 12

P=N/A, N=135, Not yet recruiting, Affiliated Hospital of Guilin Medical University; Affiliated Hospital of Guilin Medical University

P=N/A, N=359, Completed, The First Affiliated Hospital of Dalian Medical University; The First Affiliated Hospital of Dalian Medical University

P2, N=60, Not yet recruiting, Fujian Cancer Hospital; Fujian Cancer Hospital

P1, N=388, Recruiting, Shanghai Chest Hospital; CSPC Megalith Biopharmaceutical Co., Ltd

P1, N=92, Not yet recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

P2, N=100, Active, not recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Recruiting --> Active, not recruiting | Trial completion date: Nov 2025 --> Mar 2028 | Trial primary completion date: Nov 2022 --> Mar 2025

The tumor growth inhibitory rate was 99.36% for dabrafenib, trametinib, and osimertinib; 99.25% for osimertinib plus vemurafenib; 98.92% for osimertinib, encorafenib, and cetuximab; and 62.83% for pemetrexed plus carboplatin. NGS analysis identified major resistance mechanisms following the triple-targeted therapy, including the EGFR-dependent pathway, EGFR and BRAF V600E-dependent pathway, and an off-target mechanism. EGFR/BRAF/MEK triple-targeted therapy is an effective and safe approach for treating EGFR-mutated NSCLC patients resistant to EGFR-TKIs with acquired BRAF V600E mutations.

The use of NGS enhances mutation detection, highlighting the need for personalized treatment approaches in NSCLC management. The varying responses to treatments among the patients emphasize the complexity of NSCLC management and the necessity for a personalized approach.

P3, N=520, Completed, Taizhou Mabtech Pharmaceutical Co.,Ltd | Active, not recruiting --> Completed

P=N/A, N=1838, Active, not recruiting, National Cancer Institute (NCI) | N=909 --> 1838

P2, N=34, Recruiting, National Cancer Institute, Naples | Trial completion date: Sep 2024 --> Sep 2025

P2, N=45, Active, not recruiting, Oslo University Hospital | Recruiting --> Active, not recruiting | Trial primary completion date: May 2024 --> May 2025

Other radiopharmaceuticals offering new theranostic avenues in thyroid cancers are also discussed, such as prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP). After decades of a "one-size fits all" approach in thyroid cancer management, molecular imaging is paving the way towards personalized medicine.

In this large, pooled nonrandomized retrospective analysis, we observed that NIVO + IPI provides longer OS than NIVO in patients with ICI treatment-naïve advanced melanoma and identifies clinical factors that appear to be associated with survival for each treatment, which may assist with treatment decision making.

The prognosis of papillary thyroid carcinoma (PTC) is highly dependent on gene mutations and pathologic features.The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations.These mutations have been suggested to be associated with an increased risk of recurrence,poorer efficacy of postoperative radioactive iodine therapy,and reduced survival.The pathologic subtypes of PTC include classic,follicular,tall cell,hobnail,columnar cell,diffuse sclerosing,solid/trabecular,oncocytic,Warthin-like,clear cell,and spindle cell subtypes,which have different aggressiveness and linked with varied clinical prognosis.Therefore,detecting the gene mutations and pathologic subtypes of PTC is of great importance for therapeutic regimen selection and prognosis evaluation.Ultrasound imaging with non-invasiveness,convenience,and high resolution has become the primary examination method for the diagnosis and treatment of thyroid cancer.This paper reviews the correlations of gene mutations and pathologic subtypes with the ultrasound features of PTC,aiming to give new insights into the application of ultrasound imaging in predicting gene mutations and pathologic subtypes of PTC before surgery as well as provide new ideas for accurate assessment of preoperative prognosis.

P1, N=108, Active, not recruiting, Lyell Immunopharma, Inc. | Recruiting --> Active, not recruiting

P=N/A, N=909, Active, not recruiting, National Cancer Institute (NCI) | N=1917 --> 909

P=N/A, N=30, Recruiting, John Kirkwood | Not yet recruiting --> Recruiting

P2, N=24, Active, not recruiting, Providence Health & Services | Recruiting --> Active, not recruiting | N=40 --> 24