Clinical Research Directory

A Real-World, Single-Arm Study Protocol of Disitamab Vedotin in Combination With Immunotherapy and Multimodal Radiation Therapy for HER2-Positive Advanced Gastric Cancer: After Second-Line Treatment Failure

Patients with HER2-positive advanced gastric cancer who have failed standard first-line and second-line therapies have limited treatment options. Disitamab vedotin, a novel anti-HER2 antibody-drug conjugate, has been approved in China for this patient population. Additionally, immune checkpoint inhibitors (ICIs) have become a cornerstone of treatment for advanced gastric cancer, but disease progression or immune-related adverse events often lead to treatment discontinuation, raising the clinical question of immunotherapy rechallenge. Preclinical and early clinical evidence suggests that disitamab vedotin may modulate the tumor immune microenvironment and synergize with PD-1 blockade. Furthermore, multimodality radiotherapy (MMRT), combining low-dose radiotherapy (LDRT) and stereotactic body radiotherapy (SBRT), may enhance systemic anti-tumor responses by releasing tumor antigens and remodeling the immune microenvironment. This prospective, single-center, multicenter, non-interventional study aims to evaluate the efficacy and safety of disitamab vedotin in combination with PD-1 inhibitor immunotherapy and multimodality radiotherapy in patients with HER2-positive advanced gastric cancer after failure of first- and second-line treatment. Eligible patients will receive disitamab vedotin and PD-1 inhibitor per standard clinical guidelines, followed by MMRT targeting at least two independent lesions. The primary endpoint is progression-free survival (PFS) assessed by RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profile. Exploratory biomarker analyses will be conducted using tumor tissue and peripheral blood samples. A total of 30 patients will be enrolled. This study is conducted in compliance with the Declaration of Helsinki and relevant Chinese regulations, with approval from the West China Hospital Ethics Committee and written informed consent from all participants.

SHR-A1811 for Subjects With Her2-positive Gastric Cancer and Gastroesophageal Junction Adenocarcinoma After Progression on or After First-line Anti-HER2 Therapy-containing Regimen

This study will assess the efficacy and safety of SHR-A1811 compared with treatment chosen by the investigator in participants with HER2-positive (defined as immunohistochemistry \[IHC\] 3+ or IHC 2+/in situ hybridization \[ISH\]+) gastric or GEJ adenocarcinoma (based on \[American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines who have progressed on or after a first-line anti-HER2 therapy-containing regimen.