▎WuXiEdited by Kant Content Team

AstraZeneca and Daiichi Sankyo recently announced that Enhertu (trastuzumab deruxtecan), their jointly developed key antibody-drug conjugate (ADC), achieved positive results in the Phase III clinical trial DESTINY-Gastric04. In patients with HER2-positive unresectable and/or metastatic gastric or gastroesophageal junction adenocarcinoma, Enhertu demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), the primary endpoint, compared to active control in second-line treatment. At the pre-specified interim analysis, the Independent Data Monitoring Committee recommended unblinding the trial early based on Enhertu’s positive efficacy. The press release stated,Enhertu is the first HER2-targeted therapy to significantly improve overall survival in HER2-positive gastric cancer patients as a second-line treatment in a randomized Phase 3 clinical trial.

DESTINY-Gastric04 is a global, randomized, open-label Phase 3 clinical trial designed to evaluate the efficacy and safety of Enhertu versus the anti-VEGFR-2 antibody ramucirumab plus paclitaxel in patients with HER2-positive unresectable and/or metastatic gastric or gastroesophageal junction adenocarcinoma whose disease has progressed after receiving a trastuzumab-containing regimen. The primary endpoint is overall survival, and secondary endpoints include investigator-assessed progression-free survival, objective response rate, duration of response, disease control rate, and safety.

Enhertu is an ADC therapy jointly developed by AstraZeneca and Daiichi Sankyo. It is designed using Daiichi Sankyo's proprietary DXd ADC technology platform, consisting of a humanized monoclonal antibody targeting HER2 connected to a topoisomerase 1 inhibitor payload via a cleavable tetrapeptide linker.Enhertu was first approved by the U.S. FDA in 2019 for the treatment of patients with unresectable or metastatic HER2-positive breast cancer. In April 2024, the FDA approved this therapy for adult patients with unresectable or metastatic HER2-positive solid tumors who have received prior treatment and lack satisfactory alternative treatment options. Previous press releases noted that Enhertu is the first HER2-targeted ADC therapy with a tumor-agnostic indication.

Gastric cancer is the fifth most common cancer globally and the fifth leading cause of cancer-related deaths. The prognosis for gastric cancer is poor, especially in the advanced stage, with a five-year survival rate of 5% to 10%. Approximately one-fifth of gastric cancers are considered HER2-positive. The press release noted that historically, after disease progression in first-line treatment for metastatic HER2-positive gastric cancer, no HER2-targeted therapies have demonstrated a survival benefit in second-line treatment in randomized clinical trials.

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