The US Food and Drug Administration (FDA) has approved two Jazz Pharmaceuticals regimens containing Ziihera (zanidatamab-hrii) for the first-line treatment of adults with unresectable, locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive gastroesophageal adenocarcinoma (GEA).
The regimens include Ziihera combined with Tevimbra (tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2+ immunohistochemistry (IHC) 3+ or IHC 2+/in situ hybridisation (ISH)+.
The other regimen includes Ziihera with fluoropyrimidine- and platinum-containing chemotherapy for those with HER2+ IHC 3+.
The decision follows results from the Phase III HERIZON-GEA-01 trial, which demonstrated significant improvements in both progression-free survival and overall survival for patients receiving Ziihera-based treatments.
In the trial, the regimen featuring Ziihera, tislelizumab-jsgr and chemotherapy reduced the risk of death by 28% compared to a trastuzumab-based regimen, resulting in a median overall survival of 26.4 months versus 19.2 months.
Median progression-free survival with the new regimens was 12.4 months, compared to 8.1 months for trastuzumab plus chemotherapy.
The study found these benefits across subgroups defined by region and programmed death-ligand 1 (PD-L1) status.
Jazz Pharmaceuticals research and development executive vice-president and chief medical officer Rob Iannone said: “This approval is a major step forward for people with HER2+ advanced GEA.
“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.”
The trial identified diarrhoea as the most common adverse reaction, which generally appeared early and was managed with antidiarrheals and dose modifications. Few patients discontinued Ziihera due to side effects.
GEA encompasses cancers of the stomach, gastroesophageal junction, and oesophagus.
Ziihera, a bispecific HER2-directed antibody developed through collaborative efforts between Jazz Pharmaceuticals and BeOne Medicines under licence from Zymeworks, is also indicated in the US for treatment of previously treated unresectable or metastatic HER2+ biliary tract cancer.
In June, Jazz Pharmaceuticals and AbCellera signed a preclinical research, option, and licence agreement for the discovery and development of T-cell-engaging multi-specific antibodies, or T-cell engagers, for gastrointestinal cancers and other solid tumours.
