Immunotherapy has established the new standard for first-line treatment of advanced or metastatic gastric cancer. However, current second-line options-predominantly consisting of targeted therapy plus chemotherapy or chemotherapy alone-confer only modest clinical benefit. Notably, pivotal phase III second-line trials (REGARD, RAINBOW, RAINBOW-Asia, FRUTIGA) exclusively enrolled patients who progressed on chemotherapy regimens; thus, high-quality evidence guiding second-line treatment specifically for immunotherapy-refractory patients remains scarce, representing a significant unmet medical need.
Anti-angiogenic agents have demonstrated capacity to ameliorate the hypoxic, immunosuppressive tumor microenvironment while exerting synergistic anti-tumor effects when combined with immune checkpoint inhibitors. Exploratory studies evaluating immunotherapy combined with anti-angiogenic therapy plus chemotherapy in advanced gastric cancer patients after first-line failure have yielded encouraging efficacy signals (NCT03966118, NCT04982276), with objective response rates of 30-40% and median progression-free survival approaching 6 months.
Based on this, the investigators aim to evaluate the efficacy and safety profile of fruquintinib combined with nab-paclitaxel and Iparomlimab and Tuvonralimab Injection (a novel bispecific antibody) as second-line treatment for patients with advanced gastric cancer who have experienced disease progression during or after first-line immunotherapy-containing regimens.
≥ 18 years
Pathologically or cytologically confirmed diagnosis of gastric cancer (GC) or gastroesophageal junction (GEJ) cancer.
Failure of first-line treatment with PD-1/PD-L1 inhibitors
With measurable lesions according to RECIST 1.1 criteria.
History of gastrointestinal perforation and/or fistula within 6 months prior to the first dose of study medication.
Uncontrolled pleural, pericardial, or peritoneal effusions requiring repeated drainage.
Hypersensitivity to any component of monoclonal antibodies, fruquintinib, or albumin-bound paclitaxel.
Severe adverse reactions to prior immunotherapy.
Dai, Guanghai
Lead sponsor
Chinese PLA General Hospital
Sponsor institution