FDA Approves a New First Treatment for HER2-Positive Stomach and Esophageal Cancer

The U.S. Food and Drug Administration has approved two regimens built around Ziihera (zanidatamab-hrii) as a first treatment for adults with HER2-positive gastroesophageal adenocarcinoma that cannot be removed by surgery or has spread. Zymeworks Inc., the Vancouver company that discovered the drug, announced the approval on Aug. 25; its partner Jazz Pharmaceuticals holds it.

The disease covers cancers of the stomach, the esophagus and the junction between them. HER2 is a protein on some tumor cells, and the two regimens are split by how much of it a lab test finds. Ziihera with Tevimbra (tislelizumab-jsgr) and fluoropyrimidine- and platinum-based chemotherapy is approved for tumors testing IHC 3+ or IHC 2+/ISH+; Ziihera with chemotherapy alone is approved for IHC 3+ tumors, according to Zymeworks. The three-drug regimen is approved regardless of PD-L1 status, a separate marker used to select patients for immunotherapy.

The approval rests on the Phase 3 HERIZON-GEA-01 trial, published in the New England Journal of Medicine and first presented at the ASCO gastrointestinal cancers meeting this year, the company says. The release carries no survival figures. Its only statement about how well the regimen worked is a quotation from Jaffer A. Ajani of the University of Texas MD Anderson Cancer Center: "The median overall survival of more than two years observed with this regimen is encouraging and represents meaningful progress for patients and their families." Zymeworks says the trial is still running, with further analyses planned.

This is zanidatamab's second FDA approval. The drug already has accelerated approval for previously treated HER2-positive biliary tract cancer, which the release says may depend on confirmatory trials. It is a bispecific antibody: one antibody that binds two separate sites on HER2 at once.

Zymeworks cites published estimates that gastroesophageal cancers are the fifth most common cancer worldwide, that about 20% of patients have HER2-positive disease, and that fewer than 10% of those with metastatic disease survive five years.

The approval triggers a $250 million milestone payment to Zymeworks from Jazz, the company says, with up to $1.3 billion in further milestones and royalties of 10% to 20% on net sales.