DESTINY-Gastric05 Phase III Trial of Enhertu (trastuzumab deruxtecan) initiated in patients with previously untreated HER2 Positive advanced gastric cancer- Daiichi Sankyo

 The first patient has been dosed in the DESTINY-Gastric05 phase IIII trial evaluating Enhertu (trastuzumab deruxtecan) in combination with a fluoropyrimidine chemotherapy (5-FU or capecitabine) and Merck’s  anti-PD-1 therapy Keytruda (pembrolizumab) versus trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab in previously untreated patients with unresectable, locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) cancer with PD-L1 CPS ≥1..

DESTINY-Gastric05 is a global, multicenter, randomized, open-label, phase III trial  (NCT06731478) evaluating the efficacy and safety of Enhertu  (5.4 mg/kg) in combination with a fluoropyrimidine-based chemotherapy (5-FU or capecitabine) and Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) versus trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab in approximately 576 previously untreated patients with unresectable, locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or GEJ cancer  with PD-L1 CPS ≥1. An exploratory cohort of 150 patients with PD-L1 CPS <1 will be randomized to either Enhertu  plus fluoropyrimidine (5-FU or capecitabine) or trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine). The primary endpoint is progression-free survival (PFS) as assessed by blinded independent central review. The key secondary endpoint is overall survival. Additional secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response and safety.

"Following the positive overall survival results seen with DESTINY-Gastric04 in the second-line HER2 positive metastatic gastric cancer setting, the DESTINY-Gastric05 trial will explore the role of ENHERTU earlier in the metastatic setting as a first-line treatment,” said Dr. Mark Rutstein, Global Head, Oncology Clinical Development, Daiichi Sankyo. “With DESTINY-Gastric05, we are evaluating whether a potential platinum-free chemotherapy regimen of ENHERTU combined with immunotherapy and a fluoropyrimidine chemotherapy can further improve survival in patients with previously untreated HER2 positive metastatic gastric cancer.”