Jazz Pharmaceuticals has received US Food and Drug Administration (FDA) approval for two Ziihera (zanidatamab-hrii)-containing regimens for the first-line treatment of adults with unresectable locally advanced or metastatic HER2-positive (HER2+) gastroesophageal adenocarcinoma (GEA).
The approved regimens include Ziihera in combination Tevimbra(tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2+ IHC 3+ or IHC 2+/ISH+ tumours, and Ziihera plus fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2+ IHC 3+ tumours.
“Ziihera is now the first and only bispecific HER2-targeted antibody combined with a PD-1 inhibitor and chemotherapy approved for all HER2+ advanced GEA patients, regardless of PD-L1 status, establishing a new standard of care in first-line treatment,” said Rob Iannone, executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals.
The approval is based on results from the Phase 3 HERIZON-GEA-01 trial. Both Ziihera-containing combinations significantly improved progression-free survival (PFS) in the overall HER2+ population, reducing the risk of disease progression or death by 35 per cent and extending median PFS to 12.4 months compared with 8.1 months with trastuzumab plus chemotherapy.
In the overall HER2+ population, Ziihera plus tislelizumab-jsgr and chemotherapy also demonstrated a statistically significant and clinically meaningful overall survival benefit, reducing the risk of death by 28 per cent compared with trastuzumab plus chemotherapy. The regimen achieved a median overall survival of 26.4 months versus 19.2 months, representing an improvement of more than seven months and the longest median overall survival reported in a Phase 3 trial in HER2+ advanced GEA.
Progression-free survival and overall survival benefits were generally consistent across major prespecified subgroups, including geographic region and PD-L1 status.
According to Jazz Pharmaceuticals, the trial remains ongoing, with additional analyses planned.
Zanidatamab is being evaluated in multiple clinical trials as a targeted treatment option for patients with solid tumours that express HER2. The molecule is being developed by Jazz Pharmaceuticals and BeOne Medicines under license agreements with Zymeworks, which originally developed zanidatamab.
Gastroesophageal adenocarcinoma, which includes gastric, gastroesophageal junction and oesophageal cancers, is the fifth most common cancer worldwide and remains associated with poor outcomes despite advances in treatment. Approximately 20 per cent of patients have HER2+ disease, the company noted.
