FDA approved Ziihera (zanidatamab-hrii) for HER2-Positive Gastroesophageal Adenocarcinoma and Biliary Tract CancerFDA approved new drug Ziihera for two types of cancer

FDA From the archive Source published November 20, 2024 Summary added August 30, 2026 DOI ↗ Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

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Key Takeaway

Consider Ziihera for HER2-positive GEA or BTC, but confirm HER2 status with FDA-authorized tests and monitor for diarrhea and infusion reactions.

The FDA has approved Ziihera (zanidatamab-hrii), a bispecific HER2-directed antibody, for two distinct indications. In gastroesophageal adenocarcinoma (GEA), Ziihera is approved in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab-jsgr, as first-line treatment for adult patients with HER2-positive (IHC 3+ or IHC 2+/ISH+) unresectable locally advanced or metastatic disease. Additionally, Ziihera is approved as a single agent for adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), under accelerated approval based on overall response rate and duration of response.

This approval provides a new targeted option for patients with HER2-positive GEA, a population with limited first-line targeted therapies beyond trastuzumab. For BTC, an aggressive cancer with few treatment options after progression, Ziihera offers a biomarker-driven therapy. Clinicians should note that patient selection requires FDA-authorized tests to confirm HER2 status, and that the BTC indication is contingent on confirmatory trials.

＋ Clinical Details (Mechanism · Dosing · Trial Data · Warnings)

Mechanism of Action

Ziihera is a bispecific HER2-directed antibody that binds to two distinct epitopes of HER2, potentially leading to enhanced receptor binding and antitumor activity. The exact mechanism of action is not fully described in the label.

Indication & Patient Population

Ziihera is indicated for: - Gastroesophageal Adenocarcinoma (GEA): In combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab-jsgr, for first-line treatment of adult patients 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-authorized test. - Biliary Tract Cancer (BTC): As a single agent for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as detected by an FDA-authorized test. This indication is approved under accelerated approval based on overall response rate and duration of response.

Dosing & Administration

- For GEA: Patients weighing less than 70 kg: Ziihera 1,800 mg intravenously every 3 weeks or 1,200 mg every 2 weeks, in combination with chemotherapy, with or without tislelizumab-jsgr. Patients weighing 70 kg or greater: 2,400 mg every 3 weeks or 1,600 mg every 2 weeks. - For BTC: Ziihera 20 mg/kg intravenously every 2 weeks. - Premedicate all patients 30 to 60 minutes prior to each dose with acetaminophen, an antihistamine, and a corticosteroid to reduce infusion-related reactions. - For patients receiving Ziihera with chemotherapy, administer loperamide 4 mg twice daily beginning on Day 1 for at least 7 days during the first cycle for diarrhea prophylaxis. If Grade 1 or higher diarrhea occurs, continue prophylaxis in subsequent cycles. - When given with fluorouracil-containing regimens, administer fluorouracil as an intravenous infusion, not as a bolus, due to potential increase in diarrhea. - For missed doses: If a planned dose is delayed or missed, administer as soon as possible if 7 days or fewer have passed; if more than 7 days, withhold and resume on day 1 of the next cycle.

Key Clinical Trial Data

Trial data for the GEA indication are not available in the label. For BTC, the accelerated approval was based on overall response rate and duration of response, but specific efficacy data are not provided in the label.

Warnings & Contraindications

- Infusion-related reactions: Premedication is required to reduce risk. - Diarrhea: Prophylaxis with loperamide is recommended during the first cycle; severe diarrhea may occur. - No contraindications are listed in the label.

Place in Therapy

Ziihera provides a new HER2-directed option for first-line treatment of HER2-positive GEA, in combination with chemotherapy and potentially with tislelizumab-jsgr. For BTC, it is a single-agent option for previously treated HER2-positive disease, though confirmatory trials are required to verify clinical benefit.

The U.S. Food and Drug Administration (FDA) has approved a new drug called Ziihera (zanidatamab-hrii) for two types of cancer. This medicine is a targeted therapy that attacks cancer cells with a specific marker called HER2. It is given as an infusion through a vein.

Ziihera is approved for two groups of patients. First, it is for adults with a type of stomach or esophagus cancer called gastroesophageal adenocarcinoma that is HER2-positive and has spread or cannot be removed by surgery. It is used as the first treatment, together with chemotherapy, and sometimes with another drug called tislelizumab-jsgr. Second, it is for adults with a rare and aggressive bile duct cancer that is HER2-positive and has already been treated but has spread or cannot be removed.

This approval is important because it gives more options for these cancers. For stomach cancer, there were few targeted treatments beyond an older drug. For bile duct cancer, there were very few options after the first treatment stopped working. Ziihera works by helping the immune system attack the cancer cells.

However, there is an important caveat. The approval for bile duct cancer is based on early results showing the drug shrinks tumors, but it is not yet proven to help people live longer. Confirmatory studies are still ongoing. Also, not everyone will benefit. Patients should talk to their doctor to see if Ziihera is right for them and to understand the possible side effects.

What this means for you:

Ziihera is a new targeted drug for certain HER2-positive stomach and bile duct cancers; talk to your doctor to see if it's an option.

Study Details

Study typeFda approval

PublishedNov 2024

View Original Abstract ↓

1 INDICATIONS AND USAGE ZIIHERA is a bispecific HER2-directed antibody indicated for: Gastroesophageal Adenocarcinoma (GEA) • in combination with fluoropyrimidine- and platinum-containing chemotherapy, and tislelizumab-jsgr, as first-line treatment of adult patients 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-authorized test. ( 1.1 ) • in combination with fluoropyrimidine- and platinum-containing chemotherapy, as first-line treatment of adult patients with HER2-positive (IHC 3+) unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, as detected by an FDA-authorized test. ( 1.1 ) Biliary Tract Cancer (BTC) • for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as detected by an FDA-authorized test.* ( 1.2 ) *This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ( 1 ) 1.1 Gastroesophageal Adenocarcinoma (GEA) • ZIIHERA, in combination with fluoropyrimidine- and platinum-containing chemotherapy and tislelizumab-jsgr, is indicated for the first-line treatment of adult patients 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-authorized test [see Dosage and Administration ( 2.1 )] . • ZIIHERA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with HER2-positive (IHC 3+) unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, as detected by an FDA-authorized test [see Dosage and Administration ( 2.1 )] . 1.2 Biliary Tract Cancer (BTC) ZIIHERA, as a single agent, is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-authorized test [see Dosage and Administration ( 2.1 )] . This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14.2 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

FDA approved Ziihera (zanidatamab-hrii) for HER2-Positive Gastroesophageal Adenocarcinoma and Biliary Tract CancerFDA approved new drug Ziihera for two types of cancer

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FDA approved Ziihera (zanidatamab-hrii) for HER2-Positive Gastroesophageal Adenocarcinoma and Biliary Tract CancerFDA approved new drug Ziihera for two types of cancer

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