FDA Priority Review Advances HER2+ GEA Treatment Strategy

FDA has granted priority review to a supplemental biologics license application (sBLA) for tislelizumab (Tevimbra) in combination with zanidatamab (Ziihera) and chemotherapy, positioning the regimen as a potential first-line treatment option for patients with HER2-positive gastroesophageal adenocarcinoma (GEA). The application was submitted by BeOne Medicines and is supported by phase 3 data that indicate a statistically significant improvement in overall survival (OS) in this difficult-to-treat cancer.¹

GEA, which includes cancers of the stomach, gastroesophageal junction, and esophagus, remains associated with poor prognosis, particularly in advanced or metastatic settings. Approximately 20% of cases are HER2-positive, and treatment outcomes have seen limited improvement over the past decade, which highlights ongoing unmet clinical need.²

Could combination immunotherapy shift first-line treatment in HER2-positive GEA?

The sBLA is based on interim results from a global phase 3 trial (HERIZON-GEA-01), which evaluated zanidatamab plus chemotherapy, with and without tislelizumab, compared with trastuzumab plus chemotherapy. The addition of tislelizumab to the combination regimen resulted in a median OS of 26.4 months, compared with 24.4 months for zanidatamab plus chemotherapy alone and 19.2 months in the control arm.¹

“These findings represent an unprecedented survival outcome in this patient population,” said Mark Lanasa, MD, PhD, chief medical officer, Solid Tumors, BeOne Medicines, in a company press release.¹ “HERIZON GEA 01 has the potential to shift the treatment paradigm in this historically difficult-to-treat disease, with the [Tevimbra]-containing arm demonstrating an unprecedented 26-month survival benefit.”

Progression-free survival also improved in both zanidatamab-containing arms, with a median of 12.4 months compared with 8.1 months in the control group. Notably, the survival benefit was observed regardless of programmed cell death ligand-1 expression status, which may suggest broader applicability across patient subgroups.¹

What role could bispecific antibodies and checkpoint inhibitors play in this setting?

Zanidatamab is a bispecific HER2-targeted antibody designed to bind two distinct extracellular sites on the HER2 receptor, while tislelizumab is a programmed cell death protein 1 inhibitor engineered to enhance immune response against tumors. The combination reflects a growing interest in pairing targeted therapies with immuno-oncology agents to enhance antitumor activity.³

Safety findings from the trial were consistent with known profiles of the individual agents, and no new safety signals were identified. These data may support the feasibility of combining multiple biologic mechanisms within a single treatment regimen, although further evaluation will be required as regulatory review progresses.¹

How might regulatory pathways like Project Orbis affect global access?

BeOne Medicines indicated plans to submit the HERIZON-GEA-01 data through Project Orbis, an FDA-led initiative designed to facilitate concurrent review of oncology therapies across multiple international regulatory agencies. This pathway may enable more rapid global access to new treatments, particularly for cancers with limited therapeutic options.¹

From an industry perspective, priority review designation shortens FDA’s review timeline and is typically granted to therapies that may offer significant improvements in safety or effectiveness. The addition of breakthrough therapy designation for the zanidatamab-based regimen further underscores regulatory interest in the approach.

The broader implications of these findings may extend beyond gastroesophageal cancers. The combination of bispecific antibodies and immune checkpoint inhibitors represents an evolving strategy in oncology drug development, particularly for tumors with historically low responsiveness to standard therapies.⁴

While the results suggest a potential advancement in first-line treatment for HER2-positive GEA, further data and regulatory decisions will determine the extent to which this regimen becomes integrated into clinical practice. For now, the findings contribute to ongoing efforts to improve survival outcomes in a disease for which progress has been incremental.¹

References

1. BeOne Medicines. US FDA grants priority review to BeOne Medicines’ TEVIMBRA in first-line HER2+ GEA. Published April 29, 2026. Accessed April 30, 2026. https://ir.beonemedicines.com/news/us-fda-grants-priority-review-to-beone-medicines-tevimbra-in-first-line-her2-gea/2dd4da40-4943-4a0a-ad05-81899dc06d7d
2. Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-84. doi: 10.1007/s10120-014-0402-y
3. Ribas A, Wolchok JD. Combining cancer immunotherapy and targeted therapy. Curr Opin Immunol. 2013;25(2):291-6. doi: 10.1016/j.coi.2013.02.011
4. Zhang T, Lin Y, Gao Q. Bispecific antibodies targeting immunomodulatory checkpoints for cancer therapy. Cancer Biol Med. 2023;20(3):181–195. doi: 10.20892/j.issn.2095-3941.2023.0002