FDA Accepts sBLA for Zanidatamab Combinations in First-Line HER2-Positive Gastroesophageal Adenocarcinoma

The U.S. Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application (sBLA) for zanidatamab (Ziihera)–based combinations for the first-line treatment of adult patients with HER2-positive unresectable locally advanced or metastatic gastric, gastroesophageal junction (GEJ) or gastroesophageal adenocarcinoma (GEA), according to a press release from Jazz Pharmaceuticals.¹ The application was granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) target action date of August 25, 2026. The submission is supported by data from the phase 3 HERIZON-GEA-01 trial evaluating zanidatamab combinations in this setting.

HERIZON-GEA-01 trial results show benefit of zanidatamab in HER2-positive gastroesophageal cancer

Findings from HERIZON-GEA-01 demonstrated that zanidatamab in combination with standard chemotherapy improved clinical outcomes in patients with HER2-positive GEA. The addition of the PD-1 inhibitor tislelizumab to zanidatamab plus chemotherapy further enhanced clinical benefit, according to the press release.¹

Efficacy was observed in both PD-L1–positive and PD-L1–negative tumors, marking the first immuno-oncology combination to demonstrate benefit across both subgroups in this disease setting. For oncology nurses, these results are notable for treatment planning discussions and supporting patients across varying biomarker profiles.

Zanidatamab in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab, has received Breakthrough Therapy designation from the FDA. This designation is intended to expedite development and review of therapies that may offer meaningful improvement over current standard options for patients with serious disease.

The application is also being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program, which allows for earlier submission and review of clinical data to potentially accelerate access to new therapies in practice settings.

HERIZON-GEA-01 phase 3 trial design and HER2-positive GEA patient population

HERIZON-GEA-01 (NCT05152147) is a global, randomized, open-label phase 3 trial evaluating zanidatamab-based regimens compared with trastuzumab plus chemotherapy as first-line treatment.

The study enrolled 914 patients across approximately 300 sites in more than 30 countries. Eligible patients had unresectable locally advanced, recurrent or metastatic HER2-positive GEA, including adenocarcinomas of the stomach, esophagus and GEJ. HER2 positivity was defined as immunohistochemistry (IHC) 3+ or IHC 2+ with in situ hybridization (ISH) positivity confirmed by central testing.

Patients were randomized to 1 of 3 treatment arms: zanidatamab plus chemotherapy and tislelizumab, zanidatamab plus chemotherapy or trastuzumab plus chemotherapy. Dual primary end points include progression-free survival (PFS) assessed by blinded independent central review and overall survival (OS).

Zanidatamab safety profile: side effects and oncology nursing considerations

Zanidatamab has several important safety considerations relevant to oncology nursing practice, particularly in infusion centers and during ongoing treatment monitoring.

Embryo-fetal toxicity is a known risk with HER2-directed therapies. Pregnancy status should be confirmed prior to initiation, and patients should be counseled on effective contraception during treatment and for 4 months following the last dose.

Cardiac toxicity, including decreased left ventricular ejection fraction (LVEF), has been reported. In clinical studies, LVEF decline greater than 10% to below 50% occurred in 4.3% of 233 patients, and 0.9% required permanent discontinuation.¹ Baseline and periodic cardiac monitoring are recommended.

Infusion-related reactions (IRRs) occurred in 31% of patients receiving zanidatamab monotherapy, including grade 3 events in 0.4%. Most IRRs occurred on the first day of infusion, and 97% resolved within 1 day.¹ Nurses play a key role in premedication administration, infusion monitoring and rapid response to symptoms.

Diarrhea was reported in 48% of patients, with grade 3 events in 6%.¹ Early patient education, symptom monitoring and timely intervention are important components of nursing care.

Serious adverse reactions occurred in 53% of patients in a study of HER2-positive biliary tract cancer, including biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%) and fatigue (2.5%). A fatal case of hepatic failure was reported.¹

The most common adverse events (≥20%) included diarrhea, infusion-related reactions, abdominal pain and fatigue, underscoring the importance of proactive symptom management and interdisciplinary coordination in oncology nursing practice.

References

1. Jazz Pharmaceuticals plc. Jazz Pharmaceuticals announces FDA acceptance and priority review of supplemental biologics license application for Ziihera (zanidatamab-hrii) combinations in first-line HER2-positive locally advanced or metastatic GEA. PR Newswire. April 27, 2026.