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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: Toripalimab (240mg day1, Q3W*3cycle); Drug: Diphenhydramine; Drug: Platinum-based chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Tianjin Medical University Cancer Institute & Hospital
    • Contact: Shengguang Wang; Phone Number: 86022-23340123-3220; Email: wangshengguang@tjmuch.com
    • Principal Investigator: Shengguang Wang
    • Principal Investigator: Jie Xu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tori+D; Diphenhydramine combined with Toripalimab plus standard platinum-based chemotherapy as perioperative treatment	Drug: 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; Drug: 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.; Drug: 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
Other: Tori; Toripalimab plus standard platinum-based chemotherapy as perioperative treatment.	Drug: 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; Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathological complete response (pCR) rate	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to 5 years
Objective response rate (ORR)	Up to 1 year
Event-free survival (EFS)	Up to 5 years
Major pathological response rate (MPR)	Up to 1 year
Incidence of Treatment-Related Adverse Events	Up to 2 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 30, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: January 14, 2026
• First Submitted That Met QC Criteria: January 14, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Inorganic Chemicals; Benzene Derivatives; Ethylamines; Benzhydryl Compounds; Diphenhydramine; Platinum Compounds; toripalimab
• Other Study ID Numbers: TH1RA-NSCLC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No