A Randomized, Controlled, Phase-II Trial of Neoadjuvant QL1706 (Iparomlimab /Tuvonralimab) Combined With SOX Versus SOX Alone Followed by Curative Gastrectomy in Patients With Locally Advanced Diffuse-Type Gastric Adenocarcinoma
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR) rate
概览
简要总结
The goal of this randomized, open-label, phase II clinical trial is to determine whether adding the PD-1/CTLA-4 bispecific antibody QL1706 to standard SOX chemotherapy increases the pathological complete response rate in adults aged 18-75 years with resectable, locally advanced, diffuse-type, HER2-negative gastric adenocarcinoma (cT3-4aNxM0). Participants will be randomly assigned (1:1) to receive 3-4 neoadjuvant cycles of QL1706 plus SOX or SOX alone every 3 weeks, followed by curative-intent gastrectomy with D2 lymphadenectomy, and will be monitored post-operatively every 3 months for 2 years and every 6 months thereafter for recurrence, survival, and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diffuse-type gastric adenocarcinoma (Lauren classification) with signet-ring cells ≥ 50 % of tumor volume HER2-negative by IHC or ISH per ASCO/CAP guidelines Clinical stage cT3-4aNxM0 (AJCC 8th ed.) on baseline EUS + contrast-enhanced CT/MRI; disease judged resectable by multidisciplinary team No prior gastric surgery, chemotherapy, radiotherapy, or immunotherapy for cancer Age 18-75 years; ECOG performance status 0-1 Adequate organ function (ANC ≥ 1.5 × 10⁹/L, platelet ≥ 100 × 10⁹/L, Hb ≥ 9 g/dL, ALT/AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN, creatinine ≤ 1.5 × ULN and calculated CrCl ≥ 60 mL/min, INR/PT ≤ 1.5 × ULN) within 14 days before randomization Left-ventricular ejection fraction ≥ 50 % by echocardiography; no clinically significant ECG abnormalities Negative serum β-hCG pregnancy test ≤ 7 days of first dose for women of child-bearing potential; agreement to use effective contraception through 6 months post-surgery Life expectancy ≥ 6 months Signed informed consent; able to comply with study procedures and follow-up
排除标准
- •Mixed or intestinal Lauren histology; mucinous or hepatoid variants Active gastrointestinal bleeding or endoscopic evidence of major vessel invasion Other malignancy within 5 years (except curatively treated basal-cell carcinoma, cervical carcinoma in situ, or superficial bladder cancer) Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTLA-4, or other T-cell co-stimulatory/antagonist agents Autoimmune disease requiring systemic immunosuppression within 2 years (e.g., prednisone \> 10 mg/day equivalent) Receipt of live vaccine ≤ 30 days before first dose Known HIV-positive, active hepatitis B (HBsAg+ and HBV-DNA \> 200 IU/mL), or hepatitis C infection (HCV RNA positive) Active tuberculosis or history of incompletely treated TB Severe cardiovascular disease: NYHA class ≥ II heart failure, unstable angina, myocardial infarction ≤ 6 months, uncontrolled arrhythmia, or uncontrolled hypertension (systolic \> 160 mmHg or diastolic \> 100 mmHg) Peripheral neuropathy ≥ grade 2 per NCI-CTCAE v5.0 Pulmonary disease requiring systemic steroids (e.g., ≥ grade 2 pneumonitis) or oxygen therapy Active infection requiring systemic antibiotics, antivirals, or antifungals ≤ 7 days before first dose Known hypersensitivity to oxaliplatin, fluoropyrimidines, or Chinese hamster ovary cell-derived products Pregnancy or lactation Concurrent participation in another interventional clinical trial Any condition that, in the investigator's opinion, would compromise safe completion of protocol therapy or accurate assessment of outcomes
研究组 & 干预措施
QL1706+SOX
QL1706 (Iparomlimab/Tuvonralimab) 5 mg/kg intravenous infusion on day 1 plus SOX (S-1 40-60 mg orally twice daily days 1-14 and oxaliplatin 130 mg/m² intravenous infusion on day 1) every 3 weeks for 3-4 cycles before curative gastrectomy.
干预措施: QL1706 (Iparomlimab/Tuvonralimab) (Drug)
QL1706+SOX
QL1706 (Iparomlimab/Tuvonralimab) 5 mg/kg intravenous infusion on day 1 plus SOX (S-1 40-60 mg orally twice daily days 1-14 and oxaliplatin 130 mg/m² intravenous infusion on day 1) every 3 weeks for 3-4 cycles before curative gastrectomy.
干预措施: SOX Chemotherapy (Drug)
SOX
S-1 40-60 mg orally twice daily days 1-14 and oxaliplatin 130 mg/m² intravenous infusion on day 1 every 3 weeks for 3-4 cycles before curative-intent gastrectomy.
干预措施: SOX Chemotherapy (Drug)
结局指标
主要结局
Pathological complete response (pCR) rate
时间窗: Perioperative
Pathological complete response (pCR) rate, defined as the proportion of participants who achieve ypT0N0 (absence of viable tumor cells in the resected primary tumor and all examined lymph nodes, Mandard TRG 1 or Becker grade 1) after completion of 3-4 cycles of protocol-specified neoadjuvant therapy and subsequent curative-intent gastrectomy, assessed by central review of H\&E-stained slides according to AJCC 8th edition criteria within 4 weeks of surgery.
次要结局
未报告次要终点
研究者
Hao Xu
Professor
The First Affiliated Hospital with Nanjing Medical University