Toripalimab Combined With Platinum-based Chemotherapy With or Without H1 Receptor Antagonist (Diphenhydramine) in the Perioperative Treatment of Resectable Non-small Cell Lung Cancer: A Single-center, Randomized Controlled Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR) rate
研究概览
简要总结
The goal of this clinical trial is to evaluate the efficacy and safety of H1 receptor antagonist (diphenhydramine) combined with toripalimab plus standard platinum-based chemotherapy in the perioperative setting in subjects with operable NSCLC.
The subjects of this study are patients with histologically or cytologically confirmed stage II-III NSCLC (AJCC Version 9) who are planned to receive neoadjuvant therapy with toripalimab combined with standard platinum-based chemotherapy. Eligible subjects were randomized at a 1:1 ratio to receive 3-4 cycles of neoadjuvant diphenhydramine (an H1 receptor antagonist) plus toripalimab and standard platinum-based chemotherapy, or toripalimab plus platinum-based chemotherapy alone, followed by treatment response evaluation and definitive surgery. After surgery, the experimental group will receive maintenance therapy with diphenhydramine (an H1 receptor antagonist) plus toripalimab for 13-14 cycles, while the control group will receive toripalimab monotherapy for the same 13-14 cycles.
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
- •Voluntarily participate in this study, sign the informed consent form, have good compliance, and are willing to cooperate with follow-up visits;
- •Aged 18-75 years, regardless of gender;
- •ECOG performance status score of 0-1;
- •Expected survival time ≥ 3 months;
- •- Pathologically/radiologically confirmed stage II-III NSCLC (AJCC 9th Edition). For adenocarcinoma/adenosquamous carcinoma, EGFR wild-type and ALK fusion-negative required before enrollment;
- •No prior systemic anti-tumor therapy;
- •At least one measurable lesion per RECIST 1.
- •Previously irradiated lesions are measurable if progression is confirmed;
- •Adequate organ function, as evidenced by meeting the following laboratory parameters:
- •Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L without administration of granulocyte colony-stimulating factor within the past 14 days;
- •Platelet count ≥ 80 × 10⁹/L without blood transfusion within the past 14 days;
- •Hemoglobin > 8 g/dL without blood transfusion or erythropoietin administration within the past 14 days;
- •Total bilirubin ≤ 1.5 × Upper Limit of Normal (ULN);
- •Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN (for subjects with liver metastasis, AST or ALT ≤ 5 × ULN is acceptable);
- •Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate (calculated by the Cockcroft-Gault formula) ≥ 60 mL/min;
- •Adequate coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN;
- •Normal thyroid function, defined as Thyroid Stimulating Hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total triiodothyronine (T3) (or free triiodothyronine [FT3]) and free thyroxine (FT4) within the normal range are also eligible for enrollment;
- •Myocardial enzyme profile within the normal range;
- •Females of childbearing potential: negative pregnancy test (urine/serum) within 3 days pre-first dose (Cycle 1 Day 1); serum test required if urine test unconfirmed. Non-childbearing females: postmenopausal ≥ 1 year, surgically sterile or hysterectomized;
- •Subjects at risk of conception: use contraception with annual failure rate < 1% during treatment and 120-180 days post-last dose;
排除标准
- •Lung metastases from other primary malignancies;
- •Other systemic malignancies (excluding radically treated skin basal/squamous cell carcinoma or resected carcinoma in situ);
- •Current or prior myasthenia gravis;
- •Current or prior angle-closure glaucoma;
- •Current or prior benign prostatic hyperplasia;
- •Diphenhydramine allergy;
- •Pyloroduodenal obstruction, peptic ulcer-induced pyloric stenosis or bladder neck stenosis;
- •Prior radiation therapy meeting any: 1) ≥ 30% bone marrow irradiated within 14 days pre-treatment; 2) Lung lesion radiation > 30 Gy within 6 weeks pre-treatment (must recover from radiation toxicity to Grade ≤ 1, no glucocorticoids, no radiation pneumonitis history);
- •Current participation in other interventional clinical studies, or received investigational agents/devices within 4 weeks pre-first dose;
- •Systemic anti-lung cancer Chinese patent medicines or immunomodulators (thymosin, interferon, interleukin; excluding local pleural effusion control) within 2 weeks pre-first dose;
- •Active autoimmune diseases requiring systemic therapy (disease-modifying drugs, glucocorticoids, immunosuppressants) within 2 years pre-first dose (replacement therapy not considered systemic);
- •Ongoing systemic glucocorticoids (excluding topical) or immunosuppressants within 7 days pre-first dose (physiological doses: prednisone ≤ 10 mg/day or equivalent permitted);
- •Uncontrolled pleural/peritoneal effusion (eligible if no drainage needed or effusion stable 3 days post-drainage cessation);
- •Prior allogeneic organ transplantation (except corneal) or hematopoietic stem cell transplantation;
- •Inadequate recovery from prior intervention toxicities/complications (not resolved to Grade ≤ 1 or baseline, excluding fatigue/alopecia);
- •Known HIV infection (HIV 1/2 antibody positive);
- •Other conditions deemed unsuitable by investigator;
研究组 & 干预措施
Tori+D
Diphenhydramine combined with Toripalimab plus standard platinum-based chemotherapy as perioperative treatment
干预措施: Toripalimab (240mg day1, Q3W*3cycle) (Drug)
Tori+D
Diphenhydramine combined with Toripalimab plus standard platinum-based chemotherapy as perioperative treatment
干预措施: Platinum-based chemotherapy (Drug)
Tori
Toripalimab plus standard platinum-based chemotherapy as perioperative treatment.
干预措施: Toripalimab (240mg day1, Q3W*3cycle) (Drug)
Tori
Toripalimab plus standard platinum-based chemotherapy as perioperative treatment.
干预措施: Platinum-based chemotherapy (Drug)
Tori+D
Diphenhydramine combined with Toripalimab plus standard platinum-based chemotherapy as perioperative treatment
干预措施: Diphenhydramine (Drug)
结局指标
主要结局
Pathological complete response (pCR) rate
时间窗: Up to 1 year
次要结局
- Major pathological response rate (MPR)(Up to 1 year)
- Overall survival (OS)(Up to 5 years)
- Objective response rate (ORR)(Up to 1 year)
- Event-free survival (EFS)(Up to 5 years)
- Incidence of Treatment-Related Adverse Events(Up to 2 years)