NSCLC
Conditions
Brief summary
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 IIIA-IIIB 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.
Interventions
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
DRUGDiphenhydramine
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.
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
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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 IIA-IIIB 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: 1. Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L without administration of granulocyte colony-stimulating factor within the past 14 days; 2. Platelet count ≥ 80 × 10⁹/L without blood transfusion within the past 14 days; 3. Hemoglobin \> 8 g/dL without blood transfusion or erythropoietin administration within the past 14 days; 4. Total bilirubin ≤ 1.5 × Upper Limit of Normal (ULN); 5. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN (for subjects with liver metastasis, AST or ALT ≤ 5 × ULN is acceptable); 6. Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate (calculated by the Cockcroft-Gault formula) ≥ 60 mL/min; 7. Adequate coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN; 8. 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; 9. 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;
Exclusion criteria
* 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;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological complete response (pCR) rate | Up to 1 year |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
China
Outcome results
None listed