FDA clears tislelizumab plus zanidatamab for HER2-positive gastric cancer

The Food and Drug Administration has approved tislelizumab, a PD-1-blocking antibody sold as Tevimbra, in combination with the HER2-targeting antibody zanidatamab and chemotherapy as a first-line treatment for HER2-positive stomach and oesophageal adenocarcinoma [s1]. The agency recorded the approval on 25 August 2026, as supplement 18 to biologics licence application 761232, held by BeiGene [s2]. The prescribing information carrying the new indication took effect on 31 August 2026 [s1].

Tislelizumab was already cleared in the United States for oesophageal squamous-cell carcinoma and for HER2-negative gastric cancer [s1]. The new use is narrower and more specific: it applies to adults with previously untreated, unresectable, locally advanced or metastatic gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma whose tumours are HER2-positive, defined as immunohistochemistry (IHC) 3+ or IHC 2+ with a positive in-situ hybridisation test [s1]. It is given with zanidatamab and a fluoropyrimidine- and platinum-based chemotherapy regimen [s1].

What the trial tested

The approval rests on HERIZON-GEA-01, a randomised, multicentre, three-arm, open-label trial [s1]. It enrolled 914 patients, of whom 610 were randomised to the two arms the FDA used to judge efficacy: 302 received tislelizumab plus zanidatamab and chemotherapy, and 308 received trastuzumab — the long-standing HER2 antibody — plus chemotherapy [s1]. Among those patients, 434 had gastric adenocarcinoma, 134 had gastro-oesophageal junction tumours and 42 had oesophageal adenocarcinoma [s1]. The median age was 64 years, 79% were men, and 55% were Asian [s1]. Entry required a left-ventricular ejection fraction of at least 50%, a reflection of the cardiac monitoring HER2 therapy demands [s1].

In the experimental arm, tislelizumab was given at 200 mg intravenously every three weeks, alongside zanidatamab dosed by body weight — 1,800 mg for patients under 70 kg and 2,400 mg at or above that weight — and a physician's choice of two chemotherapy backbones: CAPOX, pairing oral capecitabine with intravenous oxaliplatin, or 5-fluorouracil with cisplatin, for at least six cycles [s1]. Randomisation was stratified by geographic region, HER2 status and performance status [s1]. The two co-primary endpoints were overall survival and progression-free survival assessed by blinded independent review [s1].

What it found

Tislelizumab plus zanidatamab beat the trastuzumab comparator on both measures [s1]. Median overall survival was 26.4 months versus 19.2 months, a hazard ratio of 0.72 (95% confidence interval 0.57 to 0.90; p=0.0043) [s1]. Median progression-free survival was 12.4 months versus 8.1 months, a hazard ratio of 0.63 (95% CI 0.51 to 0.78; p<0.0001) [s1]. Objective response rates were close — 67% versus 63% — but complete responses were more frequent on the new regimen (20% versus 12%), and responses lasted far longer, a median of 18.9 months against 8.3 [s1].

The most important caution is where the benefit came from. In a prespecified exploratory analysis, patients with the strongest HER2 signal (IHC 3+) drove the result: their progression-free survival hazard ratio was 0.54 (95% CI 0.43 to 0.69) [s1]. In the smaller IHC 2+/ISH-positive group, the progression-free hazard ratio was 1.08 (95% CI 0.65 to 1.78) — no advantage, and if anything a numerical disadvantage, though the confidence interval is wide [s1]. The overall-survival figures told a similar story, favouring the IHC 3+ patients [s1].

How to read it

This is a genuine survival gain in a cancer with a hard prognosis, and a four-month extension of median overall life expectancy in a first-line setting is not trivial [s1]. But the label's own subgroup data suggest the regimen's value is uneven across the HER2-positive population it covers, and the exploratory nature of that analysis means it should be read as a signal, not a verdict [s1]. The trial was open-label, so patients and investigators knew their assignment — a design that can colour subjective assessments, though overall survival is largely immune to that bias [s1].

What to watch

The practical questions now are which patients oncologists prioritise within the approved group, how tolerable the three-drug combination proves outside a trial, and whether the HER2 IHC 2+/ISH-positive subgroup is revisited as more data accrue [s1]. Zanidatamab carries its own HER2-class cautions, and the combination's safety in routine use will take time to characterise [s1].

This article describes regulatory and research news and is not medical advice. Decisions about cancer treatment are for patients and their treating oncologists.

Sources

• TEVIMBRA (tislelizumab-jsgr) prescribing information — Indications and Usage (1.3) and Clinical Studies (14.3) — U.S. Food and Drug Administration, label effective 31 August 2026
• Drugs@FDA: Tevimbra (tislelizumab-jsgr), BLA 761232, supplement 18 — approval record — U.S. Food and Drug Administration, approved 25 August 2026