Daiichi Sankyo Company, Limited and AstraZeneca announced that the first patient was dosed in DESTINYGastric06, a phase 2 trial in China evaluating the safety and efficacy of Enhertu (trastuzumab deruxtecan) in patients with HER2 positive locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma previously treated with at least two prior regimens including a fluoropyrimidine and a platinum agent.
Approximately half of all worldwide cases of gastric cancer occur in China, with about 80% of patients presenting with advanced disease at the time of diagnosis. For patients with HER2 positive metastatic gastric cancer in China, there are limited HER2 directed therapies available following disease progression with a trastuzumab-containing regimen, and more options are needed to address this continued unmet need.
“Initiation of the DESTINY-Gastric06 trial is an important step in the clinical development of Enhertu in China for the treatment of patients with HER2 positive metastatic gastric cancer,” said Gilles Gallant, BPharm, PhD, FOPQ, senior vice president, global head, oncology development, oncology R&D, Daiichi Sankyo. “Given the impressive results seen in other studies of Enhertu in this setting, we anticipate this study will further support our efforts to bring an important HER2 directed antibody drug conjugate to patients and the medical community in China.”
DESTINY-Gastric06 is an open-label, single-arm phase 2 trial in China evaluating the safety and efficacy of Enhertu (6.4 mg/kg) in patients with HER2 positive locally advanced or metastatic gastric or GEJ adenocarcinoma previously treated with at least two prior regimens including a fluoropyrimidine and a platinum agent.
The primary endpoint of DESTINY-Gastric06 is confirmed objective response rate (ORR). Secondary endpoints include investigator assessed ORR, progression-free survival, duration of response, disease control rate, overall survival, pharmacokinetics, immunogenicity and safety.
DESTINY-Gastric06 will enroll approximately 75 patients at multiple sites in China.
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fourth highest leading cause of cancer mortality. There were approximately one million new cases of gastric cancer and 768,000 deaths reported worldwide in 2020.5 Gastric cancer is typically diagnosed in the advanced stage but even when diagnosed in earlier stages of the disease the survival rate remains modest, with a five-year survival rate of 5% to 10% for advanced or metastatic disease.
Incidence rates for gastric cancer are markedly higher in eastern Asia, particularly in China, where approximately half of all worldwide cases occur. Gastric cancer is the third most common cancer in China with about 478,000 new cases and is the third leading cause of cancer-related death with approximately 374,000 deaths in 2020. Approximately 80% of patients present with advanced disease at the time of diagnosis in China.
Approximately one in five gastric cancers are considered HER2 positive. 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. HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification.
Recommended first-line treatment for HER2 positive advanced or metastatic gastric cancer in China is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy. For patients with HER2 positive metastatic gastric cancer in China, there are limited HER2 directed therapies available following disease progression with a trastuzumab-containing regimen, and more options are needed to address this continued unmet need.
Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the US only) is a HER2 directed antibody drug conjugate (ADC). Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.
Enhertu (5.4 mg/kg) is approved in Canada, EU, Israel, Japan, UK and U.S. 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 in the metastatic setting based on the results from the DESTINY-Breast01 trial.
Enhertu (6.4 mg/kg) is also approved in Israel, Japan and US for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
Enhertu is approved in the US with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
A comprehensive global development program is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers.Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
Enhertu was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the “ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers,” based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC), based on the interim results of the HER2 mutated cohort of the DESTINY-Lung01 trial.
In May 2020, Enhertu received Breakthrough Therapy Designation in the US for the treatment of patients with metastatic NSCLC whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy.
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize Enhertu in March 2019, and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.
