Trial Results Demonstrate Significant Overall Survival With Zanidatamab in Adenocarcinoma

New results from the phase 2 HERIZON-GEA-01 trial demonstrate an 84% overall survival (OS) at 18 months among patients with human epidermal growth factor receptor 2 (HER2)-expressing metastatic gastroesophageal adenocarcinoma (mGEA) who received zanidatamab, an investigational HER2-targeted bispecific antibody.

According to preliminary results, at the time of analysis, the median OS had not yet been reached, with a median duration of study follow-up of 26.5 months. The 18-month OS rate was 84%.

“Gastroesophageal adenocarcinoma represents one of the most frequent tumor types worldwide and, tragically, a leading cause of cancer-related deaths,” said lead trial investigator Elena Elimova, MD, in a press release. “Compared to what has historically been reported for OS the current approved standard of care, the OS findings from the combination of zanidatamab and chemotherapy in this trial are very compelling.”

Zanidatamab is an investigational bispecific antibody that can simultaneously bind 2 non-overlapping epitopes of HER2, known as biparatopic binding. This results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function with encouraging antitumor activity. It is being developed in multiple clinical trials for patients with HER2-expressing solid tumors.

GEA is the fifth most common cancer worldwide, and approximately 20% of patients with this diagnosis are HER2-positive. HER2-positive GEA has high morbidity and mortality, and urgently needs new treatment options.

“HER2 has been recognized as a predictive biomarker for these cancers, and it is promising to see a treatment targeting this expression exhibit strong and durable anti-tumor activity when administered with chemotherapy,” Elimova said in the press release.

The trial data include efficacy and tolerability findings from the ongoing, open-label, phase 2 study evaluating zanidatamab in combination with chemotherapy as first-line treatment for patients with advanced HER2-expressing mGEA, including gastric, esophageal, and gastroesophageal junction patients. Participants had not received prior HER2-targeted agents or systemic treatment for GEA. A total of 45 patients were enrolled.

The findings indicate that zanidatamab combined with standard chemotherapy is a highly active treatment regimen for first-line therapy of HER2-positive mGEA. In 42 patients evaluable for OS receiving zanidatamab in combination with chemotherapy, the 18-month OS rate was 84%, the 12-month OS rate was 88%, and the median OS had not yet been reached.

Furthermore, treatment with zanidatamab resulted in a confirmed objective response rate of 79% and a disease control rate of 92%. Three patients achieved complete response among 38 response-evaluable patients.

The median duration of response was 20.4 months, with a median progression-free survival of 12.5 months and 17 patients with an ongoing response at the time of data cutoff. The regimen was manageable, tolerable, and consistent with the observed safety profiles reported for other standard combination regimens for HER2-positive GEA.

“We are very encouraged by the data from this phase 2 trial, which demonstrate zanidatamab administered with chemotherapy is a highly active treatment regimen and resulted in significant and durable tumor response in the first-line setting for patients with advanced HER2-expressing mGEA,” said Rob Iannone, MD, MSCE, executive vice president and global head of research and development at Jazz Pharmaceuticals, in the press release. “These results showcase zanidatamab’s potential as a foundational treatment for patients with HER2-positive mGEA, and we look forward to additional data in 2024 from the ongoing pivotal phase 3 trial that may support US and global regulatory filings.”

Investigators are continuing to enroll patients in the phase 3 randomized HERIZON-GEA-01 trial, which is evaluating zanidatamab in combination with chemotherapy, with or without tislelizumab as a first-line treatment for HER2-expressing mGEA.

REFERENCE

Jazz Pharmaceuticals and Zymeworks Announces 84% Overall Survival at 18 Months from Phase 2 Trial Evaluating Zanidatamab in HER2-Expressing Metastatic Gastroesophageal Adenocarcinoma. News release. Jazz Pharmaceuticals; January 19, 2023. Accessed January 23, 2023. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-and-zymeworks-announce-84-overall-survival