Trastuzumab Rezetecan in Human Epidermal Growth Factor Receptor 2-Expressing Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma and Colorectal Cancer: A Multicenter, Open-Label, Phase
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- #Phase I trial
- #Antibody-drug conjugate
- #HER2-targeted therapy
- Trastuzumab Rezetecan is a novel HER2-targeted antibody-drug conjugate (ADC) tested in HER2-expressing advanced gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJ), and colorectal cancer (CRC).
- The phase I trial enrolled 100 patients (57 GC/GEJ, 43 CRC) with HER2-expressing tumors who had progressed on standard treatments.
- Dose escalation followed an i3+3 scheme (3.2, 4.8, 6.4, 8.0 mg/kg every 3 weeks), with primary endpoints being dose-limiting toxicity (DLT) and safety.
- One DLT occurred at the highest dose (8.0 mg/kg), and 66% of patients experienced grade ≥3 treatment-related adverse events (TRAEs), but only 5% discontinued due to TRAEs.
- In HER2-positive GC/GEJ (n=40), the objective response rate (ORR) was 45.0%, median progression-free survival (PFS) was 9.0 months, and median overall survival (OS) was 16.3 months.
- In HER2-positive CRC (n=37), ORR was 40.5%, median PFS was 9.5 months, and median OS was 22.7 months.
- Trastuzumab Rezetecan demonstrated tolerable safety and promising efficacy in HER2-expressing advanced GC/GEJ and CRC.