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  6. FDA approves zanidatamab-hrii and tislelizumab-jsgr for HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma
  1. Resources for Information | Approved Drugs

FDA approves zanidatamab-hrii and tislelizumab-jsgr for HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma

On August 25, 2026, the Food and Drug Administration approved zanidatamab-hrii (Ziihera, Jazz Pharmaceuticals):

  • in combination with fluoropyrimidine- and platinum-containing chemotherapy and tislelizumab-jsgr (Tevimbra, BeOne Medicines USA, Inc.), as first-line treatment for adults with HER2-positive (IHC 3+ or IHC 2+/ISH+) unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, as detected by an FDA-approved test, and
  • in combination with fluoropyrimidine-, and platinum-containing chemotherapy, as first-line treatment for adults with HER2-positive (IHC 3+) unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, as detected by an FDA-approved test.

Today, the FDA also approved two companion diagnostic devices, the PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody and the VENTANA HER2 Dual ISH DNA Probe Cocktail (Ventana Medical Systems, Inc./Roche Diagnostics), for identifying patients with HER2-positive (IHC3+ or IHC2+/ISH+) gastric, gastroesophageal junction, and esophageal adenocarcinoma for treatment with Ziihera, consistent with the approved drug labeling.

Full prescribing information for Ziihera and Tevimbra will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in HERIZON-GEA-01 (NCT05152147), a randomized, three-arm, open-label, active-comparator, global trial in patients with unresectable locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma, including those with gastric, gastroesophageal junction, and esophageal adenocarcinoma. Patients were randomized (1:1:1) to one of three treatment arms:

  • Arm A: trastuzumab with investigator’s choice of combination therapy of capecitabine and oxaliplatin (CAPOX) or fluorouracil and platinum (FP).
  • Arm B: zanidatamab-hrii in combination with CAPOX or FP.
  • Arm C: zanidatamab-hrii in combination with tislelizumab-jsgr and CAPOX or FP.

The dual major efficacy outcome measures were progression-free survival (PFS) assessed by blinded independent central review (BICR) per RECIST v1.1. and overall survival (OS).

Efficacy results showed statistically significant improvements in OS and PFS for Arm C (zanidatamab-hrii and tislelizumab-jsgr-containing arm) versus Arm A in patients with HER2 IHC3+ or IHC2+/ISH+ tumors. Median OS was 26.4 months (95% CI: 21.5, 30.3) in Arm C and 19.2 months (95% CI: 16.8, 21.8) in Arm A (hazard ratio 0.72 [95% CI: 0.57, 0.90]; p-value 0.0043) and median PFS was 12.4 months (95% CI: 9.8, 18.5) in Arm C versus 8.1 months (95% CI: 7.0, 8.9) in Arm A (hazard ratio 0.63 [95% CI: 0.51, 0.78]; p-value <0.0001).

Arm B (zanidatamab-hrii arm) showed a statistically significant improvement in PFS compared to Arm A. OS interim results were not statistically significant at the time of the PFS analysis. Based on exploratory analyses in the HER2 IHC 2+/ISH+ population, the treatment effect in Arm B was primarily attributed to the subgroup of patients with HER2 IHC 3+ tumors. In patients with IHC 3+ tumors, median PFS was 14.2 months (95% CI: 11.7, 16.7) in Arm B and 7.6 months (95% CI: 6.9, 8.5) in Arm A (hazard ratio 0.55 [95% CI 0.43, 0.69]).

The zanidatamab-hrii prescribing information includes a boxed warning for diarrhea and embryo-fetal toxicity, as well as warnings and precautions for left ventricular dysfunction and infusion-related reactions. The tislelizumab-jsgr prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

Recommended Dosage

The recommended zanidatamab-hrii dose is based on body weight. For patients with a body weight of less than 70 kg, the recommended dose is 1,800 mg every three weeks or 1,200 mg every two weeks. For patients with a body weight greater than or equal to 70 kg, the recommended dose is 2,400 mg every three weeks or 1,600 mg every two weeks. The recommended tisletizumab-jsgr dose is 150 mg every two weeks, 200 mg every three weeks, 300 mg every four weeks, or 400 mg every six weeks until disease progression or unacceptable toxicity.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Health Canada (HC) and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews are ongoing at the other regulatory agencies.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review. Zanidatamab-hrii received Fast Track, Breakthrough Therapy, and Orphan Drug designations. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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