Phase 3 Study Comparing Trastuzumab Deruxtecan Plus Chemotherapy With or Without Pembrolizumab Versus Standard Chemotherapy Plus Trastuzumab With or Without Pembrolizumab As First Treatment for Adults With Unresectable or Metastatic HER2-Positive Gastric or Gastroesophageal Junction Cancer

What this Trial Is About

Researchers are evaluating a treatment for adults with unresectable, locally advanced, or metastatic HER2-positive gastric or gastroesophageal junction GEJ cancer. The study compares the effectiveness and safety of a combination including trastuzumab deruxtecan T-DXd plus a fluoropyrimidine and pembrolizumab versus the current standard chemotherapy plus trastuzumab and pembrolizumab. The study includes a main group with PD-L1 CPS score 1 or higher and an exploratory group with PD-L1 CPS less than 1, aiming to improve first-line therapy options. Participants will be randomly assigned to one of four treatment groups the main group receives either T-DXd with fluoropyrimidine plus pembrolizumab or trastuzumab with platinum-based chemotherapy plus pembrolizumab the exploratory group receives either T-DXd with fluoropyrimidine or trastuzumab with platinum-based chemotherapy. T-DXd and pembrolizumab are given intravenously every three weeks, while chemotherapy varies between 5-FU, capecitabine, cisplatin, or oxaliplatin combinations. The study evaluates these regimens over the course of treatment to assess their impact on cancer progression. During the study, participants will have tumor samples collected to confirm HER2 and PD-L1 status and undergo imaging scans to measure tumor lesions. Heart function and lung health will be monitored to ensure safety. Researchers will assess progression-free survival and overall survival up to 59 months after randomization. Participants are expected to attend regular visits for treatment administration and safety evaluations over the treatment period and follow-up assessments according to the study schedule.

Study of TDXd, Chemotherapy, Pembrolizumab, and Trastuzumab in First-Line Metastatic HER2-Positive Gastric or Gastroesophageal Junction Cancer