What side effects are associated with this type of intervention?

Treatments for esophageal cancer, particularly those involving HER2-targeted therapies like zanidatamab, often cause side effects such as diarrhea, fatigue, nausea, and infusion-related reactions. When combined with chemotherapy agents like cisplatin and fluorouracil, additional side effects can include nausea, vomiting, decreased blood cell counts, and neuropathy. Immune checkpoint inhibitors, which may also be used, can lead to immune-related adverse events such as colitis, hepatitis, and pneumonitis.

What prior FDA approvals exist?

FDA-approved treatments for esophageal cancer include trastuzumab, which targets HER2 and is used in combination with chemotherapy for HER2-positive cases. Nivolumab, an immune checkpoint inhibitor, is approved for advanced esophageal squamous cell carcinoma after prior chemotherapy. Pembrolizumab, another immune checkpoint inhibitor, is approved for esophageal cancer with PD-L1 expression after prior treatment. These treatments are similar to the investigational use of zanidatamab, which also targets HER2 and is being studied in combination with chemotherapy.

What other types of research exist?

Promising alternatives to Zanidatamab for esophageal cancer patients include: 1) Pembrolizumab, especially for patients with high PD-L1 expression (CPS ≥10), as it has shown significant survival benefits in this subgroup. 2) Nivolumab, which has demonstrated efficacy in esophageal squamous cell carcinoma regardless of PD-L1 status. 3) Trastuzumab Deruxtecan, a novel HER2-targeted therapy that has shown promising results in HER2-positive gastric and gastroesophageal junction cancers. These alternatives should be discussed with a healthcare provider to determine the best personalized treatment plan.

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Chemotherapy

Zanidatamab + Chemotherapy ± Tislelizumab for Stomach and Esophageal Cancer (HERIZON-GEA-01 Trial)

Phase 3

Recruiting

Research Sponsored by Jazz Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, assessed within 3 days prior to randomization

Histologically confirmed unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Subjects with esophageal adenocarcinoma must not be eligible for combined chemoradiotherapy at the time of enrollment

Must not have

Prior treatment with systemic antineoplastic therapy or intraperitoneal chemotherapy for unresectable locally advanced, recurrent or metastatic GEA

Known history of or ongoing leptomeningeal disease (LMD)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3.5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing zanidatamab combined with chemotherapy, and sometimes with another drug called tislelizumab, to see if it works better than the current treatment. It targets patients with advanced HER2-positive stomach and esophageal cancers that can't be treated with surgery or standard treatments. The goal is to help the immune system find and destroy cancer cells more effectively. Zanidatamab is a novel HER2-targeting agent being evaluated for its efficacy in advanced HER2-positive cancers.

Who is the study for?

This trial is for adults with advanced HER2-positive stomach or esophageal cancers that can't be removed by surgery or have spread. Participants should be in good physical condition, with a performance status of 0-1 and proper organ function including heart health. They must not have untreated brain metastases, significant heart issues, HIV, recent other cancers, prior treatment with certain cancer drugs including HER2-targeted agents (unless it was for breast cancer over 5 years ago), or known SARS-CoV-2 infection.

What is being tested?

The study tests if zanidatamab combined with chemotherapy works better and is safer than trastuzumab plus chemotherapy in treating these cancers. Some patients will also receive tislelizumab to see if adding this drug improves outcomes. The effectiveness will be measured against the standard care for this type of cancer.

What are the potential side effects?

Possible side effects include reactions related to the immune system such as inflammation in different organs, infusion-related reactions from the drugs being administered into the bloodstream, fatigue from treatment burden on the body's resources, digestive disturbances due to impact on gastrointestinal tract functions and potential blood disorders stemming from bone marrow suppression.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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My cancer is advanced stomach or esophagus cancer that cannot be removed by surgery and tests positive for HER2.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had chemotherapy for advanced stomach or esophagus cancer that couldn't be removed by surgery.

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I have a history of or currently have leptomeningeal disease.

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I do not have serious heart conditions like uncontrolled high blood pressure or heart failure.

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I have been treated with drugs targeting immune checkpoints.

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I have a history of HIV infection.

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I have active hepatitis.

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I have another cancer that is not cured or was treated in the last 3 years.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall survival

Progression-free survival (PFS) by BICR

Secondary study objectives

Assessment of Contribution of Components based on Overall Survival

Assessment of Contribution of Components based on Progression-free Survival (PFS) by BICR

Confirmed ORR per Investigator assessment

+10 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Arm CExperimental Treatment6 Interventions

Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP

Group II: Arm BExperimental Treatment5 Interventions

Zanidatamab plus physician's choice of CAPOX or FP

Group III: Arm AActive Control5 Interventions

Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

5-Fluorouracil

2012

Completed Phase 3

~7800

Oxaliplatin

2011

Completed Phase 4

~2890

Cisplatin

2013

Completed Phase 3

~3120

Tislelizumab

2018

Completed Phase 3

~4700

Capecitabine

2013

Completed Phase 3

~3960

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for esophageal cancer, particularly HER2-positive types, often involve targeted therapies like trastuzumab and zanidatamab. These treatments work by targeting the HER2 protein, which promotes cancer cell growth. Zanidatamab, a bispecific antibody, targets two different sites on the HER2 protein, potentially offering a more effective inhibition of cancer cell proliferation compared to trastuzumab. This dual targeting mechanism is significant for patients as it may lead to better treatment outcomes, improved survival rates, and enhanced quality of life by more effectively blocking the pathways that drive cancer growth.