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

NCT07358689 | Not Yet Recruiting Phase 2

• 1 other identifier: TH1RA-NSCLC
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate

  Up to 1 year

Secondary Outcomes (5)

• 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

Study Arms (2)

Tori+D

EXPERIMENTAL

Diphenhydramine combined with Toripalimab plus standard platinum-based chemotherapy as perioperative treatment

Drug: Toripalimab (240mg day1, Q3W*3cycle); Drug: Diphenhydramine; Drug: Platinum-based chemotherapy

Tori

OTHER

Toripalimab plus standard platinum-based chemotherapy as perioperative treatment.

Drug: Toripalimab (240mg day1, Q3W*3cycle); Drug: Platinum-based chemotherapy

Interventions

Toripalimab (240mg day1, Q3W*3cycle) DRUG

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

Tori; Tori+D

Diphenhydramine DRUG

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.

Tori+D

Platinum-based chemotherapy DRUG

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

Tori; Tori+D

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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;

You may not qualify if:

• 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);

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

Location

MeSH Terms

Interventions

toripalimab; Diphenhydramine; Platinum Compounds

Intervention Hierarchy (Ancestors)

Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Inorganic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2026
• First Posted: January 22, 2026
• Study Start: January 30, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

CN (1)