MET fusion

Our findings support the potential of whole genome and transcriptome sequencing analyses as a comprehensive approach to identify treatment targets in adenocarcinoma of the stomach and the esophagus, and their application in precision oncology.

P1, N=95, Active, not recruiting, Turning Point Therapeutics, Inc. | Phase classification: P1/2 --> P1 | N=180 --> 95 | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2025 --> Jan 2024

Our case report strengthens the evidence that crizotinib may be a viable treatment option for patients with ICC with a c-MET tyrosine kinase fusion, necessitating additional clinical investigation.

Additional mutations detected in the tumor included TP53, PTEN, and a PTPRZ1-MET fusion. This represents the first reported case of a CHEK2 germline mutation in giant cell glioblastoma, further supporting the significance of impaired DNA repair mechanisms in the development of this disease.

Co-fusions involved EML4-ALK (1.9%), STRN-ALK (1.2%), and CCDC6-RET (0.7%). Conclusions Comprehensive ctDNA NGS can identify METa and associated co-alterations that may inform therapeutic decisions for patients with AC in AME.

Both larotrectinib and entrectinib are tropomyosin receptor kinase inhibitors with tissue-agnostic approvals for the treatment of patients with solid tumors harboring an NTRK fusion. To our knowledge, this is the first report of a patient with an infantile HGG receiving targeted therapy as first-line treatment with prolonged stable disease. A prospective study of larotrectinib in patients with newly diagnosed infant HGG is ongoing, and will hopefully help answer questions about durability of response, the need for additional therapies, and long-term toxicities seen with TRK inhibitors.

Multi-institutional retrospective chart review identified 83 patients with metastatic oncogene-driven NSCLC that were separated into the following two pairwise matched cohorts: (1) MET cohort (n = 41)-patients with acquired MET resistance continuing their parent TKI with a MET TKI added or (2) Chemotherapy cohort (n = 42)-patients without any actionable resistance continuing their parent TKI with a platinum-pemetrexed added...The efficacy and safety of combining MET TKIs (crizotinib, capmatinib, or tepotinib) with parent TKIs for acquired MET resistance are efficacious. Radiographic response and AEs did not differ significantly on the basis of the underlying MET TKI used. Loss of MET gene amplification, development of MET on-target mutations, Ras-Raf-MAPK alterations, and EGFR gene amplification were molecular patterns found on progression with dual parent and MET TKI combinations.

© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Moreover, our review provides an overview of and recommendations on the selection of various cross-platform technologies for the detection of MET exon 14 skipping variants, MET amplification, MET overexpression, and MET fusion. Furthermore, challenges and hurdles underlying these common detection platforms are discussed.

Since there are many types of MET alterations and related testing methods, as well as many problems and challenges during clinical testing, further sorting and standardization are required. Combined with clinical practice experience, literature review, and expert discussion, the writing group developed this consensus on the three main types of MET alterations (METex14 skipping, MET gene amplification, and MET protein overexpression) in order to guide the practical applications of clinical MET testing.

P1/2, N=180, Active, not recruiting, Turning Point Therapeutics, Inc. | Trial completion date: Nov 2023 --> Mar 2025 | Trial primary completion date: Nov 2023 --> Mar 2025

In this large, real-world multiomic characterization of age-stratified molecular differences in pancreatic ductal adenocarcinoma, YOPC is associated with a distinct molecular landscape that has prognostic and therapeutic implications.