The FDA has approved two Jazz Pharmaceuticals Ziihera-based regimens for adults with unresectable locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma, expanding the company’s use of the bispecific HER2-targeted antibody into the first-line setting.
Ziihera, or zanidatamab-hrii, is now approved with Tevimbra, or tislelizumab-jsgr, and fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2 IHC 3+ or IHC 2+/ISH+ disease, regardless of PD-L1 status. Ziihera is also approved with fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2 IHC 3+ disease.
The approval is based on the Phase 3 HERIZON-GEA-01 trial. In the overall HER2-positive population, the Ziihera, Tevimbra and chemotherapy combination reduced the risk of death by 28% compared with trastuzumab plus chemotherapy and produced median overall survival of 26.4 months, versus 19.2 months for the comparator arm.
The regimen also reduced the risk of disease progression or death by 35%, extending median progression-free survival to 12.4 months from 8.1 months with trastuzumab plus chemotherapy. Jazz said the 26.4-month median overall-survival result is the longest reported in a Phase 3 trial in HER2-positive advanced gastroesophageal adenocarcinoma.
Benefits in progression-free and overall survival were generally consistent across major pre-specified groups, including patients categorized by geographic region and PD-L1 status.
Gastroesophageal adenocarcinoma includes gastric, gastroesophageal-junction and esophageal cancers. Jazz said approximately 20% of patients have HER2-positive disease, while more than 31,000 new stomach cancer cases are diagnosed annually in the United States.
The FDA approval follows positive HERIZON-GEA-01 results reported earlier this year. It also expands on Ziihera’s prior FDA approval for previously treated unresectable or metastatic HER2-positive biliary tract cancer.
The decision comes after the FDA accepted Jazz’s supplemental biologics license application for the first-line combinations.
The Ziihera-containing regimens had a manageable safety profile consistent with prior zanidatamab studies. Diarrhea was the most common adverse reaction and generally occurred early. Patients received loperamide prophylaxis during the first treatment cycle, and diarrhea was managed with antidiarrheal medicines and treatment modifications, resulting in few Ziihera discontinuations.
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