Ventana Assay Earns CE IVDR Approval in EU as Companion Diagnostic in HER2-Expressing Breast and Biliary Tract Cancers

The VENTANA HER2 (4B5) Rabbit Monoclonal Primary Antibody RxDx assay has received CE IVDR approval for 2 label expansions in the European Union (EU).1

The assay is now indicated to identify patients with hormone receptor (HR)–positive metastatic breast cancer who have disease that is also HER2-ultralow and may be eligible for treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu). The assay is also now approved as a companion diagnostic to aid in the assessment of HER2-positive status to identify those with biliary tract cancer and a HER2 immunohistochemistry (IHC) score of 3+ who are eligible for treatment with zanidatamab-hrii (Ziihera).

“This is about creating new options for patients facing some of the toughest cancers,” Jill German, head of Pathology Lab at Roche Diagnostics, stated in a news release. “Our understanding of HER2 is rapidly evolving, and this expanded approval ensures our diagnostics are leading the way. We’re enabling clinicians to unlock personalized, life-altering treatments for patients who urgently need them.”

In the EU, T-DXd is approved as monotherapy for the treatment of adult patients with unresectable or metastatic, HR-positive, HER2-low or -ultralow breast cancer who have received at least 1 endocrine therapy in the metastatic setting and who are not considered suitable for endocrine therapy as the next line of treatment.2 Additionally, zanidatamab was approved in July 2025 as monotherapy for the treatment of adult patients with unresectable locally advanced or metastatic HER2-positive (IHC 3+) biliary tract cancer who were previously treated with at least 1 line of systemic therapy.3

How Is the Ventana Assay Used?

The Ventana assay was previously approved in Europe to identify select patients with breast cancer who may be eligible for HER2-targeted treatment with trastuzumab (Herceptin), ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or T-DXd, as well as select patients with gastric cancer who may be eligible for treatment with trastuzumab.1

The assay features standardized IHC processes from baking through staining with the goal of reducing the possibility for human error during testing. Additionally, it is designed to reduce variability that results from individual reagent dilution and other processes used with manual and semi-automated IHC tests. Ventana has demonstrated high concordance with HER2 fluorescence in situ hybridization (FISH).

In the phase 3 DESTINY-Breast06 trial (NCT04494425), which evaluated T-DXd vs investigator’s choice of chemotherapy in patients with HR-positive, HER2-low or -ultralow metastatic breast cancer who had received 1 or more lines of endocrine therapy and no previous chemotherapy in the metastatic setting, investigators also analytically validated the Ventana assay, using it to centrally determine HER2 status for patients screened for the trial.4

An analysis of the assay’s performance during the trial showed that among patient samples that had a pre-existing HER2 IHC score of 0 (n = 349), 24% were found to have HER2-low disease (IHC 1+ or IHC 2+/ISH–), 40% had HER2-ultralow disease (IHC 0 with membrane staining), and 35% had HER2-negative disease (IHC 0 without membrane staining). Furthermore, among samples from patients whose disease was previously classified as HER2-low (n = 1270), 79% were classed as HER2-low with the Ventana assay, 15% were determined to be HER2-ultralow, and 5% were HER2-negative.

Based on the outcomes of DESTINY-Breast06 and the analytical validation of the Ventana assay, study investigators concluded that rescoring and/or retesting with the Ventana assay is encouraged for patients with metastatic breast cancer whose disease is classified as HER2-negative using other methods.

References

1. Roche receives CE IVDR approval for HER2 (4B5) companion diagnostic test to identify HER2-ultralow breast cancer and biliary tract cancer patients. News release. Roche Diagnostics. September 5, 2025. Accessed September 5, 2025. https://diagnostics.roche.com/global/en/news-listing/2025/roche-receives-ce-ivdr-approval-for-her2--4b5--companion-diagnos.html
2. Enhertu, INN-trastuzumab deruxtecan. European Medicines Agency. Accessed September 5, 2025. https://www.ema.europa.eu/en/documents/product-information/enhertu-epar-product-information_en.pdf
3. Jazz Pharmaceuticals receives European Commission marketing authorization for Ziihera (zanidatamab) for the treatment of advanced HER2-positive biliary tract cancer. News release. Jazz Pharmaceuticals. July 1, 2025. Accessed September 5, 2025. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-receives-european-commission-marketing
4. Shami R, Salgado R, Bardia A, et al. Analytical and clinical validation of PATHWAY HER2 (4B5) assay for assessment of HER2-low/HER2-ultralow status and eligibility for trastuzumab deruxtecan in DESTINY-Breast06. ESMO Open. 2025;10(6):105310. doi:10.1016/j.esmoop.2025.105310