Daiichi Sankyo and AstraZeneca’s HER2-Targeted ADC Enhertu Receives First Global Approval for HER2-Positive Gastric Cancer in Japan

Daiichi Sankyo announced on the 26th that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved an expanded indication for Enhertu, a HER2-targeted antibody-drug conjugate (ADC) co-developed with AstraZeneca, for the treatment of patients with HER2-positive unresectable advanced or recurrent gastric cancer who have previously received chemotherapy but experienced disease progression. This marks the first global approval of Enhertu for the treatment of HER2-positive gastric cancer.

Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths, with a five-year survival rate of 5% for metastatic disease. In China, gastric cancer is the second most common cancer after lung cancer, accounting for 44% and 50% of global incidence and mortality, respectively. Eighty percent of Chinese patients with gastric cancer are already at an advanced stage at diagnosis, leaving limited treatment options. Approximately one-fifth of gastric cancers are HER2-positive. HER2 is a tyrosine kinase receptor expressed in many tumor types, including breast cancer, gastric cancer, and colorectal cancer.

Enhertu is an antibody-drug conjugate (ADC) designed using Daiichi Sankyo’s proprietary DXd ADC technology. It consists of a humanized monoclonal antibody targeting HER2 linked to a topoisomerase I inhibitor via a tetrapeptide linker. The drug received accelerated approval from the U.S. Food and Drug Administration (FDA) late last year for the treatment of patients with HER2-positive breast cancer. It has previously been granted Breakthrough Therapy Designation by the U.S. FDA on three occasions for the treatment of patients with HER2-positive breast cancer, gastric cancer, and non-small cell lung cancer.

The approval of Enhertu in Japan was based on the results of the open-label, randomized Phase 2 clinical trial DESTINY-Gastric01. In this trial, 187 patients with HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma were randomly assigned to receive either Enhertu or investigator’s choice of chemotherapy (irinotecan or paclitaxel).

The Enhertu treatment group achieved an objective response rate of 51.3% (95% CI: 41.9–60.5), compared with 14.3% (95% CI: 6.4–26.2) in the chemotherapy group. In the prespecified interim analysis,Patients treated with Enhertu had a 41% lower risk of death compared to those treated with chemotherapy.（HR=0.59，95% CI：0.39-0.88，p=0.0097）。The median overall survival was 12.5 months in the Enhertu group versus 8.4 months in the chemotherapy group.

References:

[1] ENHERTU® Approved in Japan for the Treatment of Patients with HER2 Positive Metastatic Gastric Cancer. Retrieved September 25, 2020, from https://www.businesswire.com/news/home/20200925005163/en

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