TEST:

HercepTest

P2, N=50, Enrolling by invitation, Tomsk National Research Medical Center of the Russian Academy of Sciences | Trial completion date: Mar 2026 --> Dec 2026

Discordance between HercepTest® and 4B5 is frequent and clinically consequential, leading to reclassification based on 4B5 that affects eligibility assessment in a substantial subset of patients. These findings highlight the need for careful interpretation of HER2 results in real-world reassessment and increased awareness of diagnostic variability in HER2-low classification.

P2, N=60, Recruiting, University of Texas Southwestern Medical Center | Trial primary completion date: Apr 2026 --> Apr 2027

P1, N=30, Recruiting, University of Texas Southwestern Medical Center | Trial completion date: Apr 2026 --> Apr 2029 | Trial primary completion date: Apr 2026 --> Apr 2028

P=N/A, N=350, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P=N/A, N=350, Not yet recruiting, AstraZeneca | Trial completion date: Jan 2026 --> Nov 2026 | Initiation date: Aug 2025 --> Apr 2026 | Trial primary completion date: Jan 2026 --> Nov 2026

P1/2, N=270, Completed, Dragonfly Therapeutics | Recruiting --> Completed | Trial completion date: Dec 2026 --> Dec 2025 | Trial primary completion date: Oct 2026 --> Dec 2025

HER2 staining was lower in 4B5 testing than in the HercepTest. Companion diagnosis using 4B5 is required to determine indications for T-DXd, especially for HER2-ultralow evaluations.

DG44 identified a significantly higher proportion of HER2-(ultra)low cases and showed the most variability in HER2 status between matched primary tumors and metastases compared to 4B5 and SP3. The choice of HER2 assay can lead to discrepancies in HER2 status assessment, which could directly influence patient eligibility for T-DXd treatment.

The developed methodologies can be used to stratify HER2 low-expression patient groups, potentially improving the interpretation of IHC assays and maximizing therapeutic benefits. This method can be implemented in histology labs without requiring a specialized workflow.

This is the first evaluation of HER2/ERBB2 expression in GBC with PBM based on WES, HercepTest, and FISH. The significant increase in ERBB2 expression, driven by the synergistic interplay between GBC and PBM, underscores a critical molecular interaction that may inform the development of targeted therapeutic strategies.

Pure ACs on the PATHWAY 4B5 platform primarily present HER2 cytoplasmic granular staining in TNAC and HER2 low expression cases. The rate of HER2 cytoplasmic granular staining on HercepTest platform was significantly lower than that of PATHWAY 4B5, and is more suitable for the detection and interpretation of HER2 0 and low expression cases.