Fam-trastuzumab deruxtecan-NXKI

BOSTON--(BUSINESS WIRE)--Boston Cell Standards today announced the publication of the CASI-01 study in Lancet: eBioMedicine demonstrating that calibration dramatically improves the accuracy and reproducibility of Immunohistochemistry (IHC) testing in breast cancer. Study authors concluded that the findings point to “pivotal advancements in precision medicine,” with potential far-reaching implications for HER2-low diagnosis, companion diagnostic development, regulatory reform for IHC clinical testing, and improved patient outcomes. Study authors concluded that the findings point to “pivotal advancements in precision medicine.” The Challenge: Inconsistent HER2-Low Testing HER2 IHC testing guides eligibility for targeted therapies such as trastuzumab and trastuzumab deruxtecan (T-DXd). However, the growing importance of identifying HER2-low tumors has revealed critical weaknesses in current testing methods. Without standardized calibration, HER2 assays often fail to consistently detect low-expression levels—leaving some patients without access to effective treatment. Test results are viewed as “no more reproducible than the flip of a coin.”1 “Patients with HER2-low cancers who could benefit from T-DXd may go untreated simply because the tests can’t measure expression levels precisely enough,” said Dr. Steve Bogen, MD, PhD, principal investigator of CASI-01 and CEO of Boston Cell Standards. “Calibration changes that. A patient’s treatment options should not depend on which lab performs their test.” Study Design and Key Findings CASI-01 is the first international study to apply IHC calibration (using IHCalibrators® from Boston Cell Standards) to evaluate HER2 testing across multiple laboratories. Results showed that calibrated IHC dramatically enhances test reliability and analytical sensitivity. The study’s findings have industry-changing implications, as they: Quantified the variability in HER2 testing across clinical laboratories; Revealed that the most widely used HER2 IHC test has poor assay dynamic range for HER2-low scores; Introduced the first objective, quantitative analytic sensitivity guidance for IHC testing; Showed that image analysis can, in some cases, outperform pathologist readouts in accuracy; Demonstrated that combining more sensitive IHC tests with image analysis improves assay dynamic range, pointing to a potential new standard in precision medicine. “As therapies expand to include HER2-low disease, the need for precise and reproducible HER2 testing has never been greater,” said Dr. Emina Torlakovic, study co-author, board-certified anatomic and clinical pathologist and hematopathologist; director of Canadian Biomarker Quality Assurance academic program; and division head of Hematopathology, Dept. of Pathology & Laboratory Medicine, Saskatchewan Health Authority and University of Saskatchewan. “Whereas current methods of IHC assay validation are insufficient to support the needs of precision medicine, by enabling an objective quantification of analytical sensitivity, we can now reliably evaluate the accuracy and precision of IHC assays for targeted therapies.” The CASI-01 study supports a long-discussed shift from viewing IHC as an “unregulated stain” to treating it as a quantitative laboratory assay.2 The research findings support recent proposals to adopt reference standards, calibration, analytic sensitivity metrics, and statistical process control—methods already routine in other diagnostic disciplines. About Boston Cell Standards Boston Cell Standards is a privately held diagnostics technology company that provides the only integrated platform for improving the accuracy and standardization of immunohistochemistry (IHC) testing used for diagnosing and treating cancer patients. BCS empowers laboratories and clinicians to deliver dependable and consistent patient test results, yielding better patient outcomes and accelerating the adoption of precision medicine. 1. Rimm D, Dacic S, Schnitt S. The Pathologists’ Conundrum. Arch Pathol Lab Med. 2023;147:17-18. https://doi.org//10.5858/arpa.2022-0226-ED. 2. Magnani B, Taylor C. Opinion: IHC should be regulated as an assay. Arch Pathol Lab Med. 2023;147:1229-1231. https://doi.org/10.5858/arpa.2023-0048-ED 2. Bell M, Chiriboga L et al. Immunohistocheistry as an assay. Letter to the editor. Journal of Histotechnology 2023; 46 (4): 156-157. https://doi.org/10.1080/01478885.2023.2278384 2. Miller DV. The chemistry in immunohistochemistry. Arch Pathol Lab Med. 2023; 147 (11): 1232-1233. https://doi.org/10.5858/arpa.2023-0254-ED

Jazz Pharmaceuticals says it will seek expanded US approval for its bispecific HER2-directed antibody Ziihera (zanidatamab-hrii) in the first half of 2026, after the drug outperformed Roche's Herceptin (trastuzumab) in a Phase III study of first-line gastroesophageal adenocarcinoma (GEA).The announcement sent Jazz shares up over 21% on Monday and lifted Ziihera licensor Zymeworks by 39%.The HERIZON-GEA-01 trial included 914 patients with HER2+, locally advanced or metastatic GEA, including cancers of the stomach, gastroesophageal junction and oesophagus. Participants were enrolled across three arms: Ziihera plus chemotherapy; Ziihera with BeOne Medicines' PD-1 inhibitor Tevimbra (tislelizumab) and chemotherapy; and a control regimen of Herceptin plus chemotherapy.Both investigational combinations met the dual primary endpoint of progression-free survival (PFS), with statistically significant improvements over the Herceptin-based comparator. Ziihera plus Tevimbra and chemotherapy also led to a significant overall survival (OS) benefit, while the Ziihera-chemo arm showed a "strong trend" in that direction at the first interim OS readout. The trial is ongoing and another OS interim analysis for Ziihera plus chemotherapy is expected in mid-2026.'Sweeping success'"While specific data were not provided in the topline release, the trial appears to be a sweeping success, showing highly statistically significant and clinically meaningful improvements," said analyst Andrew Berens of Leerink Partners.Secondary endpoints reinforced the picture. Jazz said objective response rates and duration of response improved in both Ziihera-containing arms versus the control regimen. It added that there were no new safety signals and that Ziihera's safety profile was generally consistent with the known profile of each agent."We believe these results will be practice changing," remarked Rob Iannone, Jazz's head of R&D and chief medical officer. "We expect Ziihera to become the new standard of care anti-HER2 therapy for patients with HER2+ first-line metastatic GEA regardless of PD-L1 status."The findings extend momentum from last year's US accelerated approval of Ziihera for previously treated biliary tract cancer (BTC), a decision that was supported by the Phase IIb HERIZON-BTC-01 study. It was authorised in Europe for a similar indication more recently. Confirmatory data are expected from the ongoing Phase III HERIZON-BTC-302 trial, which is assessing Ziihera plus standard-of-care therapy versus standard care alone in first-line HER2-positive advanced or metastatic BTC. That trial is expected to read out by the end of 2028, according to ClinicalTrials.gov.Ziihera brought in net sales of $8.3 million in the third-quarter, and a little over $16 million so far this year, following its launch last December.Meanwhile, Jazz is also running additional programmes of Ziihera, including the Phase III EmpowHER-303 study in metastatic HER2+ breast cancer after progression on AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) and the Phase II EmpowHER-208 study in HER2+ neoadjuvant and adjuvant breast cancer.