Two pivotal studies in targeted therapy for gastric cancer drew significant attention at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. The world’s first randomized controlled trial (RCT) of CAR-T therapy in solid tumors (Abstract #4003) produced positive results, demonstrating the superior efficacy and manageable safety profile of Claudin 18.2-targeted CAR-T compared to standard therapies. Meanwhile, the DESTINY-Gastric04 phase III trial (Abstract #LBA4002) comparing trastuzumab deruxtecan (T-DXd) to the current second-line standard of ramucirumab (RAM) plus paclitaxel (PTX) in HER2-positive unresectable/metastatic gastric cancer also reported encouraging efficacy and safety data. On-site, we invited the lead investigators—Dr. Changsong Qi from Beijing Cancer Hospital and Dr. Kohei Shitara from the National Cancer Center Hospital in Japan—for an in-depth conversation on the background, results, and clinical significance of these two studies.