Daiichi Sankyo Company, Limited announced that the European Medicines Agency has validated the Type II Variation Application for trastuzumab deruxtecan, a HER2 directed antibody drug conjugate being jointly developed by Daiichi Sankyo and AstraZeneca, for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction adenocarcinoma who have received a prior anti-HER2-based regimen. Validation confirms that the application is complete and commences the scientific review process by the EMA's Committee for Medicinal Products for Human Use . This application is based on the positive results from the DESTINY-Gastric01 pivotal phase 2 trial published in The New England Journal of Medicine and the DESTINY-Gastric02 phase 2 trial recently presented at the 2021 European Society for Medical Oncology Congress. Gastric cancer is the fifth most common cancer worldwide and the fourth highest leading cause of cancer mortality, with a five-year global survival rate of 5% to 10% for advanced or metastatic disease. 1,2,3 There were approximately one million new cases of gastric cancer and 768,000 deaths reported worldwide in 2020. 4 In Europe, approximately 136,000 cases of gastric cancer are diagnosed annually, and Eastern Europe has the second highest incidence of gastric cancer worldwide after Eastern Asia.3,4 Gastric cancer is the sixth leading cause of cancer death in Europe, and is typically diagnosed in the advanced stage but even when diagnosed in earlier stages of the disease the survival rate remains modest. Approximately one in five gastric cancers are HER2 positive. 8,9 HER2 is a tyrosine kinase receptor growth promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.9 HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification.9 Recommended first-line treatment for HER2 positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy. 10 For patients with metastatic gastric cancer that progress following initial treatment with a trastuzumab-based regimen, treatment options are limited, and in many regions in the world there are no additional HER2 directed medicines available. DESTINY-Gastric01 is a pivotal, randomized, open-label, multi-center phase 2 trial assessing the safety and efficacy of trastuzumab deruxtecan in patients from Japan and South Korea with HER2 positive advanced gastric cancer or gastroesophageal junction adenocarcinoma who have progressed on two or more prior treatment regimens including fluoropyrimidine, platinum chemotherapy and trastuzumab. Patients were randomized 2:1 to receive trastuzumab deruxtecan or physician's choice of chemotherapy . The primary endpoint of DESTINY-Gastric01 is objective response rate . Secondary endpoints include overall survival, progression-free survival, duration of response, disease control rate and time to treatment failure as well as pharmacokinetic and safety endpoints. DESTINY-Gastric01 enrolled 189 patients at multiple sites in Japan and South Korea. For more information about the trial, visit ClinicalTrials.gov. About DESTINY-Gastric02 DESTINY-Gastric02 is an open-label, single-arm, phase 2 trial in Western patients evaluating the safety and efficacy of trastuzumab deruxtecan in patients with HER2 positive metastatic and/or unresectable gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen. The primary endpoint of DESTINY-Gastric02 is confirmed ORR based on independent central review. Secondary endpoints include PFS, OS, DoR and safety. DESTINY-Gastric02 enrolled 79 patients at multiple sites in North America and Europe. For more information about the trial, visit ClinicalTrials.gov. About Trastuzumab Deruxtecan Trastuzumab deruxtecan is a HER2 directed ADC. Designed using Daiichi Sankyo's proprietary DXd ADC technology, trastuzumab deruxtecan is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca's ADC scientific platform. Trastuzumab deruxtecan consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker. Trastuzumab deruxtecan is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens based on the results from the DESTINY-Breast01 trial.