FDA Grants Priority Review to Tislelizumab/Zanidatamab in 1L HER2+ Gastric Cancers

The FDA has accepted for priority review a supplemental biologics license application (sBLA) for the combination of tislelizumab-jsgr (Tevimbra) and zanidatamab-zrjw (Ziihera) plus chemotherapy for the first-line treatment of patients with unresectable locally advanced or metastatic HER2-positive gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma, according to a news release from the developer, BeOne Medicines.¹ Notably, the FDA also granted breakthrough therapy designation to zanidatamab plus fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab, in this indication.

The sBLA was supported by primary efficacy findings from the global, pivotal phase 3 HERIZON-GEA-01 trial (NCT05152147), which evaluated zanidatamab with chemotherapy with or without tislelizumab in patients with HER2-positive unresectable locally advanced or metastatic gastroesophageal adenocarcinoma. Results from the trial were most recently shared at the 2026 ASCO Gastrointestinal Cancers Symposium.²

What were the efficacy and safety findings in the HERIZON-GEA-01 trial?

The combination of the PD-1 inhibitor tislelizumab, the HER2-targeted bispecific antibody zanidatamab, and chemotherapy met the study’s primary endpoints of progression-free survival (PFS) and overall survival (OS). The median PFS for patients receiving the tislelizumab and zanidatamab combination reached 12.4 months (95% CI, 9.8-18.5) compared with 8.1 months (95% CI, 7.0-8.9) in the control arm (HR, 0.63; 95% CI, 0.51-0.78; P <.0001). The median OS was 26.4 months (95% CI, 21.5-30.3) vs 19.2 months (95% CI, 16.8-21.8), respectively (HR, 0.72; 95% CI, 0.57-0.90; P = .0043). It was also noted that the zanidatamab combination without tislelizumab achieved a median OS of 24.4 months.

The improvement in OS and PFS was observed regardless of PD-L1 status.

Regarding safety, tislelizumab plus zanidatamab and chemotherapy demonstrated safety profiles that were generally consistent with the known effects of the components of the combination regimen. No new safety signals were identified.

Grade 3 or higher treatment-related treatment-emergent adverse effects (AEs) occurred in 71.8% of patients in the zanidatamab plus tislelizumab arm, 59% of the zanidatamab arm, and 59/6% of the trastuzumab (Herceptin) arm. Notably, treatment-related AEs led to the discontinuation of any component of treatment in 42.5%, 34.4%, and 29.1% of each arm, respectively.

How was the phase 3 HERIZON-GEA-01 trial designed?

HERIZON-GEA-01 is a randomized, open-label, multicenter phase 3 study evaluating the safety and efficacy of zanidatamab plus chemotherapy with or without tislelizumab against the standard of care. Patients were randomly assigned in a 1:1:1 ratio across 3 treatment arms to compare various combinations of targeted therapy and immunotherapy. In arm A, patients received trastuzumab and physician’s choice of chemotherapy; in arm B, they received intravenous zanidatamab plus intravenous tislelizumab and physician’s choice of chemotherapy; and in arm C, patients received zanidatamab plus intravenous tislelizumab and physician’s choice of chemotherapy. Treatment continued in 21-day cycles until disease progression, the development of unacceptable toxicity, death. Randomization was stratified based on geographic region, HER2 status, and ECOG performance status.

What patient eligibility criteria were required for the HERIZON-GEA-01 study?

Enrollment in the trial required patients 18 years and older to have histologically confirmed, HER2-positive locally advanced unresectable or metastatic adenocarcinoma of the stomach, GEJ, or esophagus.³ HER2 positivity was defined as an immunohistochemistry score of 3+ or a score of 2+ confirmed by in situ hybridization.

Participants must not have received prior treatment for locally advanced or metastatic disease or HER2-targeted treatments, though immunotherapy was permitted. Additional criteria included an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1 guidelines, and adequate organ function.

References

1. U.S. FDA grants priority review to BeOne Medicines’ TEVIMBRA in first-line HER2+ GEA. News release. BeOne Medicines. April 29, 2026. Accessed April 30, 2026. https://tinyurl.com/4z3zmnne
2. Elimova E, Rha SY, Shitara K, et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): primary analysis from HERIZON-GEA-01. J Clin Oncol. 2026;44(suppl_4):LBA285. doi:10.1200/JCO.2026.44.2_suppl.LBA285
3. A study of zanidatamab plus chemotherapy plus or minus tislelizumab in patients with HER2-positive advanced or metastatic gastric and esophageal cancers (HERIZON-GEA-01). ClinicalTrials.gov. Updated April 17, 2026. Accessed April 30, 2026. https://tinyurl.com/mwzjtcsy