PDUFA Date

FDA priority review of Jazz's Ziihera in first-line gastric cancer nears Aug. 25 decision

The sBLA rests on HERIZON-GEA-01, the only Phase 3 trial testing a HER2-directed regimen in this first-line population, with Breakthrough Therapy designation already in hand.

By AppliedXLJuly 13, 2026Trial NCT05152147

Executive Summary

The FDA is weighing a first-line approval for a HER2-targeted regimen in gastric and esophageal cancer, a decision that would extend an existing HER2 franchise into new territory rather than establish an unproven mechanism.
The application already carries two of the FDA's stronger positive signals, which raises the bar for what a delay or rejection would need to explain.
No other program has reached Phase 3 testing a HER2-directed therapy in this exact first-line population, leaving the regimen to define the standard rather than displace one.
The trial's dual primary endpoints, survival and progression-free survival, have not been posted publicly, so the decision itself will be the first confirmation of what the pivotal data showed.

The application

The FDA accepted Jazz Pharmaceuticals' supplemental Biologics License Application for Ziihera (zanidatamab-hrii) with Priority Review, setting a PDUFA target action date of August 25, 2026. The application covers zanidatamab combined with chemotherapy, with or without the PD-1 inhibitor tislelizumab (Tevimbra), for adults with HER2-positive unresectable locally advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma. The submission is under review through the FDA's Real-Time Oncology Review program, which the agency built to speed review of drugs already showing efficacy and safety signals. Rob Iannone, Jazz's chief medical officer, called the underlying trial "practice changing" and said adding tislelizumab "further enhanced clinical benefit" and marked the first immuno-oncology combination to show efficacy across both PD-L1-positive and PD-L1-negative tumors in this setting. Jazz

Probability of Success

Endpoint Met100%

Completes64%

Clinical Significance100%

Regulatory83%

The trial behind it

The application rests on HERIZON-GEA-01 (NCT05152147), a global, randomized, open-label Phase 3 trial run jointly with BeOne Medicines that enrolled 920 patients across sites in more than 30 countries, including China, Japan, South Korea, Spain, France, Italy, and Brazil. Patients were randomized to zanidatamab plus chemotherapy and tislelizumab, zanidatamab plus chemotherapy alone, or trastuzumab plus chemotherapy. The trial registers dual primary endpoints, overall survival and progression-free survival by blinded independent central review, against the trastuzumab-chemotherapy comparator that has anchored first-line HER2-positive GEA treatment. The trial reached Active, not recruiting status in April 2025 after enrollment settled at 920, and its primary completion date is registered as July 31, 2026. NCT05152147+1

Regulatory footing

The FDA granted zanidatamab Breakthrough Therapy designation for this first-line combination, a designation the agency reserves for therapies that, based on preliminary evidence, may offer improvement over available therapies on clinically significant endpoints. The program also carries a longer run of Fast Track designations dating to 2021 and an Orphan Drug designation granted in 2024, both signaling the FDA's recognition of unmet need in this population. Combined with the Priority Review status now attached to the sBLA, the application enters review with more of the agency's positive procedural signals than most oncology submissions carry at this stage. Jazz

The competitive field

No other industry-sponsored trial has reached Phase 3 testing a HER2-targeted therapy specifically in this first-line HER2-positive GEA population, making HERIZON-GEA-01 the only Phase 3 asset in that specific target-by-indication pairing. The broader HER2-directed field is active elsewhere, with antibody-drug conjugates such as trastuzumab deruxtecan and BL-M07D1 advancing in breast and lung cancers and bispecific antibodies such as anbenitamab in Phase 3 testing for gastric cancer, but none of those programs target this first-line GEA population directly. Overall HER2-target trial activity has slowed markedly in this indication, with three recent trials against 88 older ones, a decline that leaves zanidatamab's regimen with limited direct precedent to be measured against beyond the standing trastuzumab-chemotherapy comparator it was designed to beat.

What the decision will test

A priority-review sBLA built on a randomized, active-comparator Phase 3 trial with dual primary endpoints is designed to produce a decision-grade signal: whether zanidatamab's regimen improves overall survival and progression-free survival against trastuzumab-based chemotherapy in a population defined by central HER2 testing and preserved cardiac function. Jazz disclosed that a second interim overall survival analysis for the doublet regimen (zanidatamab plus chemotherapy, without tislelizumab) is expected around mid-2026, ahead of or alongside the FDA action date, which would be the first public confirmation of the magnitude of benefit the agency is evaluating. NCT05152147+1

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.