Detailed results from the positive DESTINY-Gastric02 Phase II trial showed that ENHERTU®(fam-trastuzumab deruxtecan-nxki), the AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) HER2-directed antibody drug conjugate (ADC) provided a clinically meaningful and durable tumor response in patients with HER2-positive metastatic and/or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma previously treated with a trastuzumab-containing regimen. Results were presented during a late-breaking mini-oral presentation at the European Society for Medical Oncology (ESMO) Congress 2021. Gastric cancer is associated with a poor prognosis, particularly in the advanced stages of the disease, with only 5% to 10% of metastatic patients surviving five years globally.

Approximately one in five gastric cancers are HER2-positive. In the primary analysis of DESTINY-Gastric02, the first trial of ENHERTUspecifically in Western patients with HER2-positive metastatic gastric cancer or GEJ adenocarcinoma, ENHERTU (6.4 mg/kg) demonstrated a confirmed overall response rate (ORR) of 38% as assessed by independent central review (ICR). Three (3.8%) complete responses (CR) and 27 (34.2%) partial responses (PR) were observed in patients treated with ENHERTU.

After a median follow-up of 5.7 months, the median duration of response (DoR) of ENHERTU was 8.1 months (95% CI 4.1-NE). The median progression-free survival (PFS) was 5.5 months (95% CI 4.2-7.3). An exploratory endpoint of confirmed disease control rate (DCR) of 81% (95% CI; 70.6-89.0) was seen.

The overall safety profile of ENHERTU in DESTINY-Gastric02 was consistent with that seen in DESTINY-Gastric01. The most common Grade 3 or higher drug-related treatment-emergent adverse events seen in DESTINY-Gastric02 were anemia (7.6%), neutropenia (7.6%), nausea (3.8%) and fatigue (3.8%). There were six cases (7.6%) of treatment-related interstitial lung disease (ILD) or pneumonitis reported, as determined by an independent adjudication committee.

The majority (83%) were low Grade (Grade 1 or Grade 2), with one Grade 5 (ILD or pneumonitis-related death). ENHERTUis approved in Israel, Japan and the US for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial. ENHERTU is being further assessed in a comprehensive clinical development program evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.

Several presentations featured during the ESMO Congress 2021 will showcase the strength and depth of ENHERTUdata across multiple tumor types, including gastric, lung and breast cancers, reinforcing the transformational potential of this medicine in the treatment of HER2-targetable cancers.