HER-2 YVMA

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

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=45, Completed, IFCT

Introduction: HER2 (ERBB2) is a target for various anti-cancer therapies, including large (Trastuzumab deruxtecan) or small molecules (Neratinib). An AI-powered pan-cancer image analysis of HER2 IHC of tumor cells in conjunction with genomic data reveals a positive correlation between ex20ins and S310x ERBB2 mutation and protein expression. This correlation is also seen at the RNA level, but the lesser levels relative to ERBB2 amplified cases suggests the effect may be mediated at the protein level.

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

P2, N=46, Completed, Intergroupe Francophone de Cancerologie Thoracique | Active, not recruiting --> Completed

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

P2, N=46, Active, not recruiting, Intergroupe Francophone de Cancerologie Thoracique | Trial completion date: Jul 2023 --> Feb 2024

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.

Additionally, ELVN-002 in combination with ado-trastuzumab emtansine (T-DM1) or trastuzumab deruxtecan (T-DXd) exhibited increased anti-tumor activity in vivo compared to either drug alone.Non-clinical data suggests ELVN-002 has a favorable pharmacokinetic (PK) profile and low risk of QTc prolongation. The trial opened for enrollment in February 2023.Study sponsor: Enliven Therapeutics. NCT0565087