HER-2 A775

Of total cohort, 18 patients (72.0 %) underwent intrathecal pemetrexed (ITP), with a median survival time of 7.4 months (95.0 % confidence interval, 3.3-11.6) from the initiation of ITP to death...Our results highlight CSF cfDNA NGS's potential in LM resistance understanding and ITP efficacy prediction. MET CNG positively impacts survival for ITP recipients, whereas the coexistence of EGFR T790M and EGFR-independent resistance mechanisms leads to poor outcomes.

P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

Finally, phase II clinical trials involving HER2-altered NSCLC patients demonstrated promising treatment outcomes with trastuzumab deruxtecan, trastuzumab emtansine, pyrotinib, pyrotinib + apatinib and trastuzumab + pertuzumab + docetaxel. In conclusion, the prevalence of HER2 alteration among Malaysian NSCLC patients falls within the global range. A systematic review of clinical trials revealed promising treatment outcomes and Malaysian NSCLC patients with HER2 alterations are anticipated to similarly benefit from HER2-targeted therapies.

Notably, EGFR ex20 insertions exhibited greater insertion diversity. Clinical characteristics of EGFR and ERBB2 ex20 NSCLC were similar, characterized by low tumor mutation burden (TMB), a predominant never-smoker population, and a majority of lung adenocarcinoma cases.

P2; Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

The derivatives with the pyrido[2,3,4-de]quinazoline core displayed superior efficacy of antiproliferation in BaF3 cells harboring HER2insYVMA mutation compared with afatinib and neratinib. Oral administration of 4a and 10e (30 mg/kg, QD) displayed significant antitumor efficacy in an in vivo xenograft model. We proposed promising strategies for the development of HER2insYVMA mutant inhibitors in this study.

P2, N=102, Active, not recruiting, AstraZeneca | Trial completion date: Jan 2028 --> Jul 2026

MSI-high was observed in 15 samples. Conclusions Comprehensive ctDNA NGS can identify ERBB2m including complex insertions and co-alterations that may inform therapeutic decisions for patients with AC in AME.

P1, N=30, Recruiting, National Cancer Institute (NCI) | N=18 --> 30

In heavily pretreated pts with limited Tx options, T-DXd demonstrated encouraging anticancer activity and long DoR across multiple tumor types with HER2m and a range of HER2 expression levels, with a known safety profile. Translational research will help characterize pts who may derive greatest benefit from T-DXd.

42.8% of pts received antibody-drug conjugates targeting ERBB2 in further lines of therapy, trastuzumab emtansine (37.1%) and Trastuzumab Deruxtecan (5.7%). ERBB2 mts in NSCLC are rare. In this comprehensive retrospective real-world multicenter cohort of Latin American NSCLC pts, the frequency of ERBB2 mutations was identified in 2,8% of patients. The most common ERBB2 mutation identified was A775_G776insYVMA, similar to what is reported in the literature.