AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been granted Orphan Drug Designation (ODD) in the US for the treatment of patients with gastric cancer, including gastroesophageal junction cancer.
An estimated 27,600 new cases of gastric cancer will be diagnosed this year and the disease could lead to more than 11,000 deaths in the US in 2020.
The Food and Drug Administration (FDA) grants ODD to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US.
In the Phase II DESTINY-Gastric01 trial, patients with HER2-positive metastatic gastric or gastroesophageal cancer who were treated with Enhertu, a HER2-directed antibody drug conjugate (ADC), demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR), the primary endpoint, and overall survival (OS), a key secondary endpoint, versus patients treated with investigator’s choice of chemotherapy (irinotecan or paclitaxel monotherapy).
The overall safety and tolerability profile of Enhertu (6.4mg/kg) in DESTINY-Gastric01 was consistent with that seen in the Phase I gastric cancer trial. The most common adverse events were haematologic and gastrointestinal including neutrophil count decrease, anaemia, nausea and decreased appetite. There were cases of drug-related interstitial lung disease (ILD) and pneumonitis, the majority of which were Grade 1 and 2, with two Grade 3 and one Grade 4. No Grade 5 events (ILD-related deaths) occurred in patients with gastric cancer in the Phase I trial or in the Phase II DESTINY-Gastric01 trial.
Earlier this month, Enhertu received two Breakthrough Therapy Designations for its potential use in HER2-positive unresectable or metastatic gastric cancer and HER2-mutant metastatic non-small cell lung cancer. Enhertu also received SAKIGAKE designation from Japan’s Ministry of Health Labour and Welfare (MHLW) for potential use in HER2-positive gastric cancer in March 2018. A supplemental New Drug Application was recently submitted to the MHLW.
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Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality with a five-year survival rate of 5% for metastatic disease. There were approximately one million new cases reported in 2018 and 783,000 deaths. In the US, it is estimated that 27,600 new cases of gastric cancer will be diagnosed in 2020 and more than 11,000 people will die from the disease.
Approximately one in five gastric cancers are HER2 positive. HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including gastric, breast and lung cancers. Gastric cancer is usually diagnosed in the advanced stage in the US, but even when diagnosed in earlier stages of the disease the survival rate remains modest.6 Recommended 1st-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. For gastric cancer that progresses on 1st-line treatment, there are no other approved HER2-targeted medicines.
Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the US) is a HER2-directed ADC and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.
Enhertu (5.4mg/kg) is approved in the US and Japan 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 DESTINY-Breast01 trial.