A Single-Arm, Prospective, Open-Label Clinical Study of Iparomlimab and Tuvonralimab (QL1706) Combined With DOS as Neoadjuvant Therapy for Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Pathological Complete Response Rate (pCR Rate)
研究概览
简要总结
This is an open-label, prospective, interventional study designed to enroll 34 patients with locally advanced gastric or gastroesophageal junction adenocarcinoma, aiming to evaluate and observe the efficacy and safety of QL1706 in combination with DOS for the treatment of locally advanced gastric or gastroesophageal junction adenocarcinoma. Enrolled patients will receive iparomlimab and tuvonralimab in combination with the DOS regimen (docetaxel + oxaliplatin + S-1) administered in 21-day treatment cycles. Subjects who complete 3-4 cycles of treatment and are deemed suitable for surgery will undergo gastrectomy, with the specific interval between neoadjuvant therapy and surgery determined by the investigator based on actual clinical circumstances. Following surgery, clinicians will administer postoperative treatment according to the postoperative pathological assessment results and the clinical practice treatment principles of the study center. The primary endpoint is the pathological complete response rate assessed by postoperative pathological evaluation.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 75 years; male or female.
- •Previously untreated, resectable adenocarcinoma of the stomach or gastroesophageal junction (GEJ).
- •Clinical stage cT3-4a/N+ M
- •ECOG performance status 0-
- •Adequate organ function within 7 days prior to treatment, meeting the following criteria: (1) Complete blood count (CBC) criteria (without blood transfusion within 14 days): Hemoglobin (Hb) ≥ 90 g/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count (PLT) ≥ 80 × 10⁹/L; (2) Serum chemistry criteria: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 60 mL/min; (3) Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%). (4) Thyroid function: thyroid-stimulating hormone (TSH) ≤ upper limit of normal (ULN).
- •Participants of childbearing potential must agree to use effective contraception during the study period and for 6 months after study completion.
- •The participant voluntarily agrees to participate in this study and signs the informed consent form.
排除标准
- •Known history of hypersensitivity or allergy to QL1706 or its excipients, tegafur/gimeracil/oteracil (S-1), oxaliplatin, docetaxel, or any of their excipients.
- •History of another malignancy within 5 years prior to screening or concurrent malignancy, except for curatively treated carcinoma in situ of the cervix, non-melanoma skin cancer, and superficial bladder tumors.
- •Patients with distant metastasis and/or unresectable disease;
- •Prior treatment with immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents.
- •Receipt of any antineoplastic agents within 4 weeks prior to the first dose of study drug.
- •Patients with gastrointestinal disorders such as intestinal obstruction (including partial obstruction), or those with evidence or risk of gastrointestinal bleeding, perforation, or obstruction.
- •Any bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to enrollment, or unhealed wounds, ulcers, or fractures.
- •Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study.
- •Subjects requiring systemic therapy with corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive agents within 2 weeks prior to the first dose of study drug.
- •Receipt of live or live-attenuated vaccine within 4 weeks prior to the first dose of study drug.
- •Major surgery or significant trauma within 4 weeks prior to the first dose of study drug.
- •Active or history of autoimmune disease, with the exception of vitiligo or resolved childhood asthma/atopy that requires no intervention in adulthood.
- •History of immunodeficiency, including HIV infection, or other acquired or congenital immunodeficiency disorders, or history of organ transplantation or allogeneic bone marrow transplantation.
- •Subjects with inadequately controlled cardiovascular clinical symptoms or diseases.
- •Severe infection (CTCAE Grade > 2) within 4 weeks prior to the first dose of study drug.
- •Patients with a history of interstitial lung disease (except for radiation pneumonitis not treated with corticosteroids), non-infectious pneumonitis, or active pulmonary tuberculosis; or a history of active pulmonary tuberculosis within 1 year prior to enrollment, or more than 1 year prior to enrollment if not adequately treated.
- •Pregnant or breastfeeding women.
- •Other concomitant diseases that, in the opinion of the Investigator, pose a serious risk to the subject's safety or may interfere with the subject's ability to complete the study.
研究组 & 干预措施
Iparomlimab and Tuvonralimab Injection (QL1706) Plus DOS Neoadjuvant Therapy Arm
Enrolled patients receive QL1706 (5 mg/kg, IV, D1) combined with the DOS regimen (docetaxel 40 mg/m², IV, D1 + oxaliplatin 100 mg/m², IV, D1 + S-1 40 mg/m², PO, BID, D1-14), administered every 21 days per cycle for 3-4 cycles. Subjects who complete neoadjuvant therapy and are deemed suitable for surgery will undergo gastrectomy, followed by subsequent treatment based on postoperative pathological assessment.
干预措施: Tegafur-Gimeracil-Oteracil (Drug)
Iparomlimab and Tuvonralimab Injection (QL1706) Plus DOS Neoadjuvant Therapy Arm
Enrolled patients receive QL1706 (5 mg/kg, IV, D1) combined with the DOS regimen (docetaxel 40 mg/m², IV, D1 + oxaliplatin 100 mg/m², IV, D1 + S-1 40 mg/m², PO, BID, D1-14), administered every 21 days per cycle for 3-4 cycles. Subjects who complete neoadjuvant therapy and are deemed suitable for surgery will undergo gastrectomy, followed by subsequent treatment based on postoperative pathological assessment.
干预措施: Gastrectomy (Procedure)
Iparomlimab and Tuvonralimab Injection (QL1706) Plus DOS Neoadjuvant Therapy Arm
Enrolled patients receive QL1706 (5 mg/kg, IV, D1) combined with the DOS regimen (docetaxel 40 mg/m², IV, D1 + oxaliplatin 100 mg/m², IV, D1 + S-1 40 mg/m², PO, BID, D1-14), administered every 21 days per cycle for 3-4 cycles. Subjects who complete neoadjuvant therapy and are deemed suitable for surgery will undergo gastrectomy, followed by subsequent treatment based on postoperative pathological assessment.
干预措施: Iparomlimab and Tuvonralimab Injection (QL1706) (Drug)
Iparomlimab and Tuvonralimab Injection (QL1706) Plus DOS Neoadjuvant Therapy Arm
Enrolled patients receive QL1706 (5 mg/kg, IV, D1) combined with the DOS regimen (docetaxel 40 mg/m², IV, D1 + oxaliplatin 100 mg/m², IV, D1 + S-1 40 mg/m², PO, BID, D1-14), administered every 21 days per cycle for 3-4 cycles. Subjects who complete neoadjuvant therapy and are deemed suitable for surgery will undergo gastrectomy, followed by subsequent treatment based on postoperative pathological assessment.
干预措施: Docetaxel (Drug)
Iparomlimab and Tuvonralimab Injection (QL1706) Plus DOS Neoadjuvant Therapy Arm
Enrolled patients receive QL1706 (5 mg/kg, IV, D1) combined with the DOS regimen (docetaxel 40 mg/m², IV, D1 + oxaliplatin 100 mg/m², IV, D1 + S-1 40 mg/m², PO, BID, D1-14), administered every 21 days per cycle for 3-4 cycles. Subjects who complete neoadjuvant therapy and are deemed suitable for surgery will undergo gastrectomy, followed by subsequent treatment based on postoperative pathological assessment.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Pathological Complete Response Rate (pCR Rate)
时间窗: Perioperative, upon postoperative pathological evaluation
Defined as the proportion of patients with no residual tumor cells in the resected tumor tissue and regional lymph nodes upon pathological evaluation.
次要结局
- R0 Resection Rate(Perioperative, upon postoperative pathological evaluation)
- Major Pathological Response Rate (MPR Rate)(Perioperative, upon postoperative pathological evaluation)
- Objective Response Rate (ORR)(On Day 1 of every 2 cycles (each cycle is 21 days), prior to surgery)
- Disease Control Rate (DCR)(On Day 1 of every 2 cycles (each cycle is 21 days), prior to surgery)
- Number of Participants with Adverse Events (AEs) and Severity Graded(From signing of ICF through 30 days after the last dose)
- 3-Year Disease-Free Survival Rate (DFS Rate)(3 years after treatment)
研究者
Yongxu Jia
Chief Physician
The First Affiliated Hospital of Zhengzhou University