Retlirafusp Alfa Combined With Apatinib and Nab-Paclitaxel as Second-line Treatment for Patients With Immunotherapy-Pretreated Gastric or Gastroesophageal Junction Cancer: A Prospective, Single-Arm Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 50
- 试验地点
- 1
研究概览
简要总结
This is a prospective, single-arm, investigator-initiated phase II clinical study. The study evaluates the efficacy and safety of retlirafusp alfa (a PD-L1/TGF-βRII bifunctional fusion protein) combined with apatinib (a VEGFR-2 tyrosine kinase inhibitor) and nab-paclitaxel in patients with locally advanced unresectable, locally recurrent, or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma who have progressed after first-line immunotherapy-containing treatment.
详细描述
Gastric cancer is one of the most common malignant tumors of the digestive system. For patients with advanced gastric cancer who have failed first-line immunotherapy plus chemotherapy, second-line treatment options remain limited. Retlirafusp alfa is a bifunctional fusion protein targeting PD-L1 and TGF-βRII. Apatinib is a small-molecule anti-angiogenic agent. Nab-paclitaxel is a chemotherapeutic agent recommended for second-line treatment of advanced gastric cancer. This prospective, single-arm study investigates the efficacy and safety of this triple combination regimen in immunotherapy-pretreated advanced second-line gastric or gastroesophageal junction adenocarcinoma, to provide a new therapeutic option for these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide written informed consent prior to any study-specific procedures
- •Age ≥ 18 years
- •ECOG performance status 0 or 1
- •Histologically or cytologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, locally advanced unresectable, locally recurrent, or metastatic
- •Human epidermal growth factor receptor 2 (HER2) negative
- •Failed first-line immunotherapy-containing systemic treatment
- •At least one measurable lesion per RECIST Version 1.1
- •Adequate organ function:
- •Hemoglobin ≥ 90 g/L 2)Absolute neutrophil count ≥ 1.5 × 10⁹/L 3)Platelet count ≥ 80 × 10⁹/L 4)Total bilirubin < 1.5 × upper limit of normal (ULN) 5)ALT/AST < 2.5 × ULN; < 5 × ULN in patients with liver metastasis 6)Serum creatinine ≤ 1.5 × ULN or creatinine clearance > 60 mL/min 7)Urine protein < 2+ or 24-hour urine protein < 1 g 8)Left ventricular ejection fraction (LVEF) ≥ 50% 9)Coagulation function: INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN 8.Fertile male and female subjects must agree to use highly effective contraception during the study and for 6 months after the last dose of study treatment; female subjects must have a negative pregnancy test within 7 days before enrollment
排除标准
- •Known hypersensitivity to any component of the study drugs
- •Prior treatment with any VEGFR inhibitor (including apatinib, sorafenib, sunitinib)
- •Prior treatment with retlirafusp alf
- •Received any investigational drug within 4 weeks before first dose
- •Received systemic corticosteroid (> 10 mg prednisone equivalent daily) or other immunosuppressive agents within 2 weeks before first dose, except for allowed topical/inhaled use or physiological replacement
- •Active autoimmune disease or history of autoimmune disease (except controlled hypothyroidism, type 1 diabetes with stable insulin, vitiligo, resolved childhood asthma)
- •Known immunodeficiency (including HIV infection), organ transplantation, or allogeneic hematopoietic stem cell transplantation
- •Uncontrolled cardiac disease: NYHA Class ≥ II heart failure, unstable angina, myocardial infarction within 1 year, clinically significant arrhythmia requiring intervention
- •Severe infection (CTCAE Grade > 2) within 4 weeks before first dose; active pulmonary infection, interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis; active tuberculosis
- •Active hepatitis B (HBV DNA ≥ 2000 IU/mL) or active hepatitis C (HCV RNA positive)
- •History of other malignancy within 5 years before enrollment, except adequately treated basal cell carcinoma, squamous cell carcinoma of skin, or carcinoma in situ of cervix
- •Pregnant or lactating women
- •Unwilling or unable to comply with study procedures
- •Any other condition deemed inappropriate by the investigator