Tolerability and efficacy results—including the first overall survival data—from a phase II trial examining first-line zanidatamab, an investigational HER2-targeted bispecific antibody, in combination with chemotherapy for patients with HER2-expressing metastatic gastroesophageal adenocarcinoma were presented by Elena Elimova, MD, and colleagues at the 2023 ASCO Gastrointestinal Cancers Symposium (Abstract 347).
The preliminary results showed that, at the time of analysis, the median overall survival had not yet been reached, with a median follow-up of 26.5 months. The 18-month overall survival rate was 84% (95% confidence interval [CI] = 68%–93%).
“Gastroesophageal adenocarcinoma represents one of the most frequent tumor types worldwide and, tragically, a leading cause of cancer-related deaths. Compared to what has historically been reported for overall survival with the current approved standard of care, the overall survival findings from the combination of zanidatamab and chemotherapy in this trial are very compelling," said Dr. Elimova, the lead trial investigator and a medical oncologist at Princess Margaret Cancer Centre. "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 antitumor activity when administered with chemotherapy."
Elena Elimova, MD
Trial Details
The data include efficacy and tolerability findings from an ongoing, open-label phase II study (ClinicalTrials.gov identifier: NCT03929666) evaluating zanidatamab in combination with chemotherapy as first-line treatment for patients with advanced HER2-expressing metastatic gastroesophageal adenocarcinoma—a population comprised of patients with gastric, esophageal, and gastroesophageal junction cancers. Patients had not received prior HER2-targeted agents nor systemic treatment for metastatic gastroesophageal adenocarcinoma. A total of 46 patients with metastatic gastroesophageal adenocarcinoma were enrolled from 15 sites across the United States, Canada, and South Korea, and patients were administered zanidatamab with physician's choice of chemotherapy treatment (standard first-line combination therapy).
Results
The data demonstrated zanidatamab combined with standard chemotherapy is a highly active treatment regimen for first-line therapy of HER2-positive metastatic gastroesophageal adenocarcinoma. In 42 patients evaluable for overall survival receiving zanidatamab in combination with chemotherapy, the 18-month overall survival rate was 84% (95% CI = 68%–93%), the 12-month overall survival rate was 88% (95% CI = 73%–95%), and the median overall survival had not yet been reached (with 26.5 months of median follow-up). Treatment with zanidatamab resulted in a confirmed objective response rate of 79% (95% CI = 63%–90%) and a disease control rate of 92% (95% CI = 79%–98%), with 3 patients achieving complete response among 38 response-evaluable patients.
The median duration of response was 20.4 months (95% CI = 8.3 months to not evaluable), with a median progression-free survival of 12.5 months (95% CI = 7.1 months to not evaluable) with 17 patients having 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 patients with HER2-positive metastatic gastroesophageal adenocarcinoma.
Patients are currently being enrolled in a phase III randomized clinical trial, HERIZON-GEA-01 (ClinicalTrials.gov identifier: NCT05152147), evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab as a first-line treatment for HER2-expressing metastatic gastroesophageal adenocarcinoma.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
