This study is a domestic, multicenter, single-arm clinical trial designed to evaluate the efficacy and safety of heterogeneous radiotherapy (high and low dose) sequenced with iparomlimab and tuvonralimab plus SOX as a first-line treatment for unresectable locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma.
Age 18-75 years, male or female.
Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma.
Patients with no prior systemic therapy for locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. For patients who received neoadjuvant or adjuvant chemotherapy or chemoradiotherapy with curative intent, the interval from the last treatment to disease progression must be at least 6 months.
HER-2 negative (IHC 1+ or IHC 2+/FISH-negative).
Presence of other histologic components confirmed by histopathology or cytology, such as squamous cell carcinoma, undifferentiated carcinoma, neuroendocrine carcinoma, etc.
Prior treatment with any tumor immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies), immune checkpoint agonists (e.g., antibodies targeting ICOS, CD40, CD137, GITR, OX40), or immune cell therapy (e.g., CAR-T cells).
Palliative local therapy to non-target lesions within 2 weeks before the first dose; or systemic non-specific immunomodulatory therapy (e.g., interleukin, interferon, thymosin) within 2 weeks before the first dose.
Clinically significant pleural effusion, pericardial effusion, or ascites requiring frequent drainage (≥ 1 time per month).