Upcoming First-Line HER2-Positive Trials: ARTEMIDE-Gastric01, DESTINY-Gastric05, and HLX22

In this episode, Dr. Wainberg and Dr. Shah preview upcoming first-line phase 3 trials in HER2-positive metastatic gastroesophageal adenocarcinoma (GEA). Dr. Wainberg introduces DESTINY-Gastric05, which pairs trastuzumab deruxtecan (T-DXd) with 5-fluorouracil (5-FU)-based chemotherapy and immunotherapy, and notes that the goalposts keep shifting as new survival benchmarks emerge.

Dr. Shah walks through ARTEMIDE-Gastric01, which enrolls only programmed death-ligand 1 (PD-L1)-positive patients. The control arm is a KEYNOTE-811-style regimen of trastuzumab plus pembrolizumab plus chemotherapy. Two experimental arms test rilvegostomig, a programmed death-1 (PD-1)/T-cell immunoreceptor with Ig and ITIM domains (TIGIT) bispecific. One arm replaces oxaliplatin or cisplatin with T-DXd (rilvegostomig + T-DXd + 5-FU), and the other pairs rilvegostomig with trastuzumab plus chemotherapy. Dr. Shah frames the key questions as whether T-DXd can be better than trastuzumab in the first-line setting, and whether a PD-1/TIGIT bispecific offers benefit over a PD-1 inhibitor alone. He acknowledges that multiple anti-TIGIT studies, including the Skyscraper studies and a domvanalimab gastric study, were negative, but argues that HER2-positive biology may create a different context, and notes that phase 2 data for the bispecific were positive.

Dr. Wainberg also mentions HLX22, an antibody targeting a different HER2 domain from the one zanidatamab blocks, being combined with trastuzumab and running primarily out of Asia. He observes that the volume of first-line HER2-positive phase 3 activity is notable and expresses a wish for more second-line research.

In the next episode, “Patient Conversations, Global Trial Representation, and Closing Thoughts on HER2-Positive GEA,” the panel discusses patient-facing conversations, global trial enrollment, moving HER2 agents into earlier settings, and closing reflections.