Toripalimab Combined With Platinum-based Chemotherapy With or Without H1 Receptor Antagonist in the Perioperative Treatment of Resectable Non-small Cell Lung Cancer

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Toripalimab (240mg day1, Q3W*3cycle)
  Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2). Toripalimab was administered concurrently with chemotherapy, Q3W
• Препарат Diphenhydramine
  Diphenhydramine, is an antihistamine. It has antihistamine H1 receptor effects, strong inhibitory effects on the central nervous system, and atropine-like effects. Diphenhydramine was administered 20mg qd IM d0-d2.
• Препарат Platinum-based chemotherapy
  Carboplatin: AUC5 (per Calvert formula); maximum dose: 750 mg；Cisplatin: 75 mg/m² D1, Q3W; Pemetrexed: 500 mg/m² D1, Q3W; Docetaxel: 60-75 mg/m² or Paclitaxel: 175 mg/m², D1, Q3W

Первичные конечные точки

• Pathological complete response (pCR) rate [Срок оценки: Up to 1 year]

Вторичные конечные точки (5)

• Major pathological response rate (MPR) [Срок оценки: Up to 1 year]
• Overall survival (OS) [Срок оценки: Up to 5 years]
• Objective response rate (ORR) [Срок оценки: Up to 1 year]
• Event-free survival (EFS) [Срок оценки: Up to 5 years]
• Incidence of Treatment-Related Adverse Events [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• 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 1.1. 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;

Критерии исключения

• 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;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Tianjin Medical University Cancer Institute & Hospital — Тяньцзинь

Идентификаторы

NCT: NCT07358689 · TH1RA-NSCLC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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