Trastuzumab Deruxtecan Gets Orphan Drug Status for Gastric Cancer

Trastuzumab deruxtecan, an antibody—drug conjugate (ADC), has been granted Orphan Drug Designation (ODD) for the treatment of gastric cancer, including gastroesophageal junction cancer.

The drug (Enhertu) was approved by the FDA in December 2019 for unresectable or metastatic human epidermal receptor 2 (HER2)-positive breast cancer in patients who have received 2 or more prior anti-HER2-based regimens.

AstraZeneca and Daiichi Sankyo said in a statement last week that the ODD follows recent Breakthrough Therapy Designations for HER2-positive metastatic gastric cancer and HER2-mutant metastatic non-small cell lung cancer.

Trastuzumab deruxtecan is designed to delivery cytotoxic chemotherapy to cancer cells via a HER2 antibody attached to a novel topoisomerase I inhibitor payload and a tetrapeptide-based linker.

The companies said an estimated 27,600 new cases of gastric cancer will be diagnosed in 2020, with an estimated 11,000 deaths in the US. Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed earlier, survival rate is modest.

In the phase 2 DESTINY-Gastric01 trial, patients with HER2-positive metastatic gastric or gastroesophageal cancer treated with the product 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 1 gastric cancer trial.

The full results of DESTINY-Gastric-01 will be presented during the American Society of Clinical Oncology ASCO20 Virtual Scientific Program later this week.

The most common adverse events were hematologic and gastrointestinal, including neutrophil count decrease, anemia, nausea and decreased appetite. There were cases of drug-related interstitial lung disease (ILD) and pneumonitis.