A Prospective, Single-Arm, Phase Ⅱ Clinical Trial Evaluating Fruquintinib in Combination With Paclitaxel for Injection (Albumin-bound) and Iparomlimab and Tuvonralimab Injection as Second-Line Therapy in Advanced Gastric Cancer Patients Previously Received Immunotherapy
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.
• ECOG performance status of 0-1
• Expected survival ≥3 months;
• Major organ functions meet the following requirements :
‣ Absolute neutrophil count (ANC) ≥ 1,500/mm³ (1.5 × 10⁹/L) (no growth factors used within 14 days).
⁃ Platelet count (PLT) ≥ 100,000/mm³ (100 × 10⁹/L) (no correction therapy used within 7 days).
⁃ Hemoglobin (Hb) ≥ 9 g/dL (90 g/L) (no correction therapy used within 7 days).
⁃ Serum creatinine ≤ 1.5 × upper limit of normal (ULN).
⁃ Total bilirubin (BIL) ≤ 1.5 × upper limit of normal (ULN).
⁃ Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) levels ≤ 2.5 × upper limit of normal (ULN); ≤ 5 × upper limit of normal (ULN) for patients with liver metastases.
⁃ Urinalysis is normal, or urine protein \< (++), or 24-hour urine protein level \< 1.0 g.
• Normal coagulation function, with no history of active bleeding or thrombotic diseases:
‣ International normalized ratio (INR) ≤ 1.5 × ULN.
⁃ Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
⁃ Prothrombin time (PT) ≤ 1.5 × ULN.
• For patients with potential fertility, the following requirements must be met:
‣ Adopt a medically acceptable contraceptive method (e.g., intrauterine device, oral contraceptives, or condoms) during the study treatment period and for 3 months after the completion of study treatment.
⁃ Serum human chorionic gonadotropin (β-HCG) test must be negative within 72 hours prior to study enrollment.
⁃ Must not be breastfeeding.
⁃ Patients must have provided written informed consent, and be willing and able to comply with the scheduled visits, study treatment plan, laboratory tests, and other trial procedures.