TEST:

PATHWAY antiHer2/neu (4B5) Rabbit Monoclonal Primary Antibody

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

In September 2022, the US Food and Drug Administration (FDA) expanded approval of the legacy Roche monoclonal antibody 4B5-based immunohistochemistry (IHC) assay to identify patients with HER2-low breast cancers predicted to respond to trastuzumab deruxtecan (T-DXd), based on findings from the DESTINY-Breast04 and DESTINY-Breast06 clinical trials...We examine the current challenges of repurposing legacy HER2 IHC biomarker assays for HER2-low detection, evaluating the precedent of other repurposed IHC assays (ALK, CD30, and PD-L1), and emphasizing the necessity for proper technical and clinical validation before widespread implementation. We conclude that prospective clinical trials are essential to establish clinically meaningful cutoffs and analytical specifications appropriate for patient selection in HER2-low disease.

P1, N=60, Recruiting, Memorial Sloan Kettering Cancer Center

Notably, FOXA1 and RAB25 are strongly implicated in breast cancer biology, and FOXA1 has been directly linked to the aryl hydrocarbon receptor (AHR), the main regulator of CYP1A1. These results position CEU-938 as a strong precision-therapy candidate that combines target selectivity, a favorable toxicity profile, and biomarker-enabled patient stratification, with potential clinical benefit in ER+ and HER2+ enriched tumors, as well as a subset of TNBC.

However, novel methods for labeling cells with fixed amounts of proteins are needed. In addition, standards for validation of quantitative IHC methods should be developed and their clinical utility must be demonstrated.

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

Of two patients with the HER2-ultralow phenotype, one was alive with no evidence of disease at 16 months follow-up. The results support the idea that HER2/neu overexpression is exceptionally rare in LGSOC; nevertheless, future trials are essential to fully characterize the spectrum of HER2/neu alterations in LGSOC and to determine definitively whether the rare cases with mutations or ultralow expression could represent a small subgroup that might benefit from specific targeted agents.

P1, N=45, Recruiting, Baylor College of Medicine | Trial primary completion date: Dec 2025 --> Dec 2026

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.

P1, N=17, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=37 --> 17

AI-assisted interpretation improved observer agreement (Kappa: 0.703 vs. 0.610 in non-amplified cases) and reduced ambiguous immunohistochemistry (IHC) 2+/0 assignments. These findings delineate distinct clinicopathological characteristics of HER2-ultralow/null tumors, highlight HER2 IHC reproducibility challenges, and validate AI as an effective tool for standardizing scoring to optimize patient selection for T-DXd therapy.

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.