FDA Approves Companion Diagnostics for Zanidatamab-Eligible Gastroesophageal Adenocarcinoma

The FDA has approved expanded indications for the PATHWAY HER2 (4B5) immunohistochemistry (IHC) assay and the VENTANA HER2 Dual in situ hybridization (ISH) DNA Probe Cocktail, companion diagnostics that identify patients with HER2-positive metastatic gastroesophageal adenocarcinoma (GEA) who may be candidates for zanidatamab-hrii (Ziihera), the bispecific antibody whose first-line activity in this setting was established in the phase 3 HERIZON-GEA-01 trial.^1,2

Both assays, made by Roche Diagnostics, are now approved to assess HER2 status in gastric, gastroesophageal junction, and esophageal adenocarcinoma.¹ Two zanidatamab-hrii regimens, one combined with tislelizumab-jsgr (Tevimbra) and chemotherapy and the other with chemotherapy alone, are approved for first-line treatment of adults with unresectable locally advanced or metastatic HER2-positive GEA.^1,3

“GEA can be a difficult diagnosis for patients to face, with most cases only being detected once the disease has progressed to an advanced stage,” Laura Apitz, head of pathology lab at Roche Diagnostics, stated in a news release.¹ “By adding GEA to the approved indications for our widely-available HER2 assay, we expand the patient population eligible for targeted therapy and potentially improve patient outcomes.”

The approval follows HERIZON-GEA-01, a phase 3 trial that randomized 914 patients with previously untreated HER2-positive GEA 1:1:1 to zanidatamab-hrii plus tislelizumab-jsgr and chemotherapy (n = 302), zanidatamab-hrii plus chemotherapy (n = 304), or trastuzumab plus chemotherapy (n = 308).² At a median follow-up of 26 months, median progression-free survival (PFS) was 12.4, 12.4, and 8.1 months across the 3 arms, respectively (HR, 0.63 and 0.65 vs control; P < .0001 for both), with 18-month PFS rates of 43.9%, 38.0%, and 20.9%.²

Median overall survival (OS) was 26.4, 24.4, and 19.2 months (HR, 0.72 [P = .0043]; and HR, 0.80 [P = .0564]), with 24-month OS rates of 54.3%, 50.3%, and 38.8%, respectively. Objective response rates were 70.7%, 69.6%, and 65.8%, with median duration of response of 20.7, 14.3, and 8.3 months, respectivley.²

In a prespecified subgroup analysis presented at the 2026 American Society of Clinical Oncology Annual Meeting, the survival benefit with zanidatamab plus tislelizumab and chemotherapy compared with trastuzumab plus chemotherapy was consistent across PD-L1 subgroups. When assessed by PD-L1 tumor area positivity (TAP), median OS was 29.7 versus 15.8 months among patients with TAP less than 1% and 26.4 versus 21.2 months among those with TAP of 1% or greater.⁴

Safety Profile

The median treatment duration was 43.1, 31.0, and 30.0 weeks across the triplet, doublet, and control arms, respectively, and no new safety signals were identified.²

Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 71.8%, 59.0%, and 59.6% of patients across the triplet, doublet, and control arms, respectively. TRAEs led to discontinuation of zanidatamab or trastuzumab in 11.9%, 8.5%, and 2.3% of patients, respectively.^2,4

Diarrhea was the most common TRAE, occurring in 82%, 76%, and 48% of patients across the 3 arms, respectively. Grade 3 or higher diarrhea occurred in 24.8%, 20.0%, and 12.9% of patients.⁴

HERIZON-GEA-01 Trial Design

HERIZON-GEA-01 enrolled adults with previously untreated, unresectable or metastatic HER2-positive GEA, defined as IHC 3+ or IHC 2+ with ISH-confirmed amplification, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were enrolled across sites in more than 30 countries from December 2021 to February 2025.

Zanidatamab-hrii was dosed at 1800 mg for patients weighing less than 70 kg or 2400 mg for those weighing 70 kg or more, intravenously every 3 weeks. Tislelizumab-jsgr was administered at 200 mg every 3 weeks. Chemotherapy consisted of capecitabine plus oxaliplatin or fluorouracil plus cisplatin. The control arm received trastuzumab instead of zanidatamab-hrii.²

More on the Companion Diagnostic Tests

The PATHWAY HER2 (4B5) IHC assay is integrated with Roche's automated VENTANA BenchMark slide-staining platform and has demonstrated high concordance with HER2 fluorescence in situ hybridization (FISH) testing. The VENTANA HER2 Dual ISH DNA Probe Cocktail uses dual-color technology to detect HER2 gene amplification and also demonstrates high concordance with HER2 FISH testing. Both tests are already widely used in breast and gastric cancers.¹

References

1. Roche receives FDA approval for companion diagnostic tests to identify patients with HER2-positive metastatic gastroesophageal adenocarcinoma eligible for Ziihera. News release. Roche; August 26, 2026. Accessed August 27, 2026. https://tinyurl.com/w5asc993

2. Shitara K, et al. Zanidatamab with and without tislelizumab in HER2-positive gastroesophageal cancer. N Engl J Med. Published online May 27, 2026. doi:10.1056/NEJMoa2517729

3. U.S. FDA approves Ziihera (zanidatamab-hrii) with and without tislelizumab plus chemotherapy in first-line HER2+ advanced gastroesophageal adenocarcinoma. News release. Jazz Pharmaceuticals; August 25, 2026. Accessed August 27, 2026. https://tinyurl.com/4b58888e

4. BeOne Medicines announces phase 3 HERIZON-GEA data published in NEJM and presented at ASCO 2026. News release. BeOne Medicines; May 27, 2026. Accessed August 27, 2026. https://tinyurl.com/5hackr6u