New Gastric Cancer Therapy Extends Survival Beyond Two Years

SAN CARLOS, Calif. – January 06, 2026 – By George Millen

A new triple-drug combination has achieved what many thought improbable, extending the median overall survival for patients with a deadly form of advanced stomach cancer to over two years. Full results from the pivotal Phase 3 HERIZON-GEA-01 trial, announced by BeOne Medicines Ltd., show that its regimen of ZIIHERA® (zanidatamab) and TEVIMBRA® (tislelizumab) combined with chemotherapy sets a new high-water mark in a field that has seen little progress for more than a decade.

The findings, scheduled for a late-breaking oral presentation at the prestigious American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI), position the therapy as the likely new first-line standard of care for patients with HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). The data revealed a median overall survival of 26.4 months for the triple-drug arm, representing a 28% reduction in the risk of death compared to the current standard.

A New Benchmark in a Challenging Disease

For over a decade, the standard treatment for newly diagnosed HER2+ advanced GEA has been the chemotherapy-plus-trastuzumab combination, which established a median overall survival of approximately 13.8 months in the foundational ToGA trial. Numerous subsequent attempts to improve upon this benchmark have failed, leaving patients and clinicians with limited options and a grim prognosis. The HERIZON-GEA-01 trial decisively breaks this long-standing barrier.

The global, randomized study evaluated two experimental arms against the control arm of trastuzumab plus chemotherapy. Both experimental arms met the dual primary endpoint of progression-free survival (PFS), the time a patient lives without their cancer worsening. Patients receiving ZIIHERA plus chemotherapy, with or without TEVIMBRA, saw their median PFS extended to 12.4 months, a significant improvement over the 8.1 months in the control arm.

However, the most striking result came from the overall survival data in the triple-combination arm. The median overall survival of 26.4 months marks a greater than seven-month improvement over the control group. The second experimental arm, using ZIIHERA plus chemotherapy alone, also showed a strong trend towards a survival benefit with a median of 24.4 months.

“The HERIZON-GEA-01 results are encouraging, with median overall survival for tislelizumab plus zanidatamab and chemotherapy surpassing two years, an outcome that marks a significant advancement in the treatment of metastatic HER2+ gastroesophageal adenocarcinoma,” said Manish Shah, M.D., Chief of the Solid Tumor Service and Director of Gastrointestinal Oncology at Weill Cornell Medicine. “Unlike prior studies in HER2+ GEA with checkpoint blockade therapy, the addition of tislelizumab demonstrated meaningful activity even in TAP PD-L1 < 1%, suggesting a potential new treatment option for this subgroup, while broadening choices for patients with PD-L1 ≥1%.”

Overcoming a Key Hurdle: Efficacy Beyond PD-L1 Status

One of the most clinically significant findings from the trial is the combination's robust efficacy regardless of a patient's PD-L1 expression level. PD-L1 is a protein that can help cancer cells hide from the immune system. While other immunotherapy combinations, such as Keytruda plus trastuzumab, have shown benefits, their approval and effectiveness are often restricted to patients whose tumors express higher levels of PD-L1.

In the HERIZON-GEA-01 trial, approximately one-third of the 914 enrolled patients had tumors with low PD-L1 expression (TAP score <1%). In this traditionally harder-to-treat subgroup, the triple therapy demonstrated remarkable effectiveness, with a hazard ratio for overall survival of 0.49, indicating a 51% reduction in the risk of death. This potent activity in a PD-L1-low population suggests the ZIIHERA and TEVIMBRA combination could benefit a much broader patient population, simplifying treatment decisions for oncologists who may not need to wait for biomarker test results to initiate this highly effective therapy.

This broad efficacy underscores the powerful synergy between the two novel drugs. The objective response rate (ORR) for the triple combination was 70.7%, but more importantly, the median duration of that response (DOR) was an impressive 20.7 months, highlighting the durable nature of the anti-tumor effect driven by the regimen.

The Science of Synergy: How the Combination Works

The success of the HERIZON-GEA-01 trial lies in the innovative pairing of two distinct but complementary mechanisms of action. ZIIHERA is not a standard HER2-blocking antibody. It is a bispecific antibody, meaning it has two unique arms that bind to two different, non-overlapping sites on the HER2 receptor on cancer cells. This 'dual-binding' approach leads to more effective receptor clustering and removal from the cell surface, and it is believed to trigger a more potent immune response against the tumor through mechanisms like antibody-dependent cellular cytotoxicity (ADCC).

When combined with TEVIMBRA, a PD-1 inhibitor, the effect is amplified. TEVIMBRA works by blocking the PD-1 pathway, a major brake on the immune system that cancer cells exploit to evade attack. By releasing this brake, TEVIMBRA allows the body's own T-cells to recognize and kill cancer cells more effectively. The synergy appears to come from ZIIHERA marking the tumor cells for destruction, while TEVIMBRA simultaneously empowers the immune system to carry out the attack, leading to deeper and more durable responses than either approach might achieve alone.

The safety profile was deemed manageable and consistent with the known side effects of each drug class. While rates of Grade ≥3 treatment-related adverse events were higher in the triple-therapy arm (71.8%) compared to the control (59.6%), this was expected given the addition of a third agent and a longer duration of treatment. The most common significant side effect was diarrhea, but it was generally manageable and rarely led to treatment discontinuation.

Navigating the Path to Patients and Market Dominance

With these compelling results, BeOne Medicines and its partner, Jazz Pharmaceuticals, are moving swiftly to make the combination a global reality for patients. BeOne has announced its intention to submit supplemental Biologics License Applications to both the U.S. Food and Drug Administration (FDA) and China’s National Medical Products Administration (NMPA).

The global commercialization strategy is split between the two companies. Jazz Pharmaceuticals holds the rights for the U.S., Europe, and Japan, while BeOne Medicines holds the rights for most of Asia Pacific, Australia, and New Zealand. This is particularly strategic for BeOne, as the incidence of gastroesophageal cancer is highest in East Asia, representing a significant market and a region with a profound unmet medical need.

The data firmly positions the ZIIHERA-based regimens to displace a decade-old standard of care and challenge newer competitors. As the oncology community convenes for the ASCO GI symposium, the full presentation of these results is widely expected to be a main topic of discussion, heralding a true paradigm shift in how this aggressive cancer is treated from the very first line of defense.