Enhertu Shows Survival Improvement

At a planned interim analysis, the Independent Data Monitoring Committee recommended unblinding the trial based on the superior efficacy of Enhertu.

Enhertu is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%. Following disease progression in the first-line metastatic setting of HER2 positive gastric cancer, there historically have been no HER2 directed medicines that have demonstrated a survival benefit in the second-line metastatic setting in a randomized clinical trial. Enhertu is currently approved in more than 65 countries based on DESTINY-Gastric01, a randomized phase II trial, and DESTINY-Gastric02 and DESTINY-Gastric06, two single-arm phase II trials. DESTINY Gastric04 is the first phase III trial of Enhertu in HER2 positive advanced gastric cancer.

“ENHERTU is the first HER2 directed medicine to demonstrate an improvement in overall survival in a randomized phase III trial in the second-line metastatic setting of patients with HER2 positive gastric cancer, reinforcing previous findings seen in our other earlier phase gastric cancer trials,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “With these DESTINY-Gastric04 results, we will work with global regulatory authorities to seek approval in regions where Enhertu is not currently indicated as a second line option as well as work to secure full approval in regions where Enhertu is conditionally approved.”

“We are committed to advancing the care of patients with metastatic gastric cancer and continuing to understand the role of Enhertu in earlier lines of treatment,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “The results of DESTINY-Gastric04 show that second-line treatment with Enhertu can extend survival compared with a chemotherapy-based regimen and should be considered for all eligible patients with HER2 positive metastatic gastric cancer.” The safety profile seen in DESTINY-Gastric04 is consistent with the established safety profile of Enhertu. Data from DESTINY-Gastric04 will be presented at an upcoming medical meeting and shared with global regulatory authorities.

About DESTINY-Gastric04 - DESTINY-Gastric04 is a global, randomized, open-label, phase III trial evaluating the efficacy and safety of Enhertu (6.4 mg/kg) versus ramucirumab and paclitaxel in patients with HER2 positive (IHC 3+ or IHC 2+/ISH+) unresectable and/or metastatic gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen. The primary endpoint is OS. Secondary endpoints include investigator-assessed progression-free survival, objective response rate, duration of response, disease control rate and safety. DESTINY-Gastric04 enrolled 494 patients in Asia, Europe and South America.