Neoadjuvant Therapy of SBRT Sequencial With Toripalimab and Chemotherapy in Resectable Stage II-III NSCLC Patients(neoR-TORCH)

NCT06437977 | Recruiting Phase 3

• 1 other identifier: IS24056
• Study Type: interventional
• Target: 478
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, controlled, multi-center, phase III clinical study to evaluate the efficacy and safety of SBRT sequencial with Toripalimab and chemotherapy versus Toripalimab and chemotherapy for subjects with resectable, stage II-III NSCLC.

Conditions

Stage II-III Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• 2-year Event Free Survival Rate

  Event Free Survival (EFS):EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. EFS determined either by biopsy assessed by central pathologist or by imaging using RECIST 1.1 assessed by BICR.

  2 years

• pCR rate

  Pathological Complete Response (pCR) Rate :pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes following completion of neoadjuvant therapy.

  up to 7 weeks after neoadjuvant

Secondary Outcomes (9)

• Major Pathological Response

  up to 7 weeks after neoadjuvant

• Lymph node downstaging rate

  up to 7 weeks after neoadjuvant

• Perioperative complications

  90 days after the last administration

• Treatment associated adverse events

  90 days after the last administration

• EFS

  up to 3 years

Study Arms (2)

Experimental

EXPERIMENTAL

Participants receive SBRT for primary lung tumor, sequential receive totally 4 cycles of Toripalimab combined with platinum doublet chemotherapy during perioperative period ; participants receive consolidation therapy of Toripalimab Intervention: SBRT: 24Gy/3fractions; Drug: 4cycles(Toripalimab IV 240mg + platinum-based doublet chemotherapy)+13 cycles(Toripalimab IV 240mg); Biological: Toripalimab

Radiation: SBRT; Drug: Toripalimab

Active Comparator

ACTIVE COMPARATOR

Participantsreceive totally 4 cycles of Toripalimab combined with platinum doublet chemotherapy during perioperative period ; participants receive consolidation therapy of Toripalimab Intervention: Drug: 4cycles(Toripalimab IV 240mg + platinum-based doublet chemotherapy)+13 cycles(Toripalimab IV 240mg); Biological: Toripalimab

Drug: Toripalimab

Interventions

SBRT RADIATION

SBRT. 24Gy/3fractions Toripalimab 240 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1;Drug: Cisplatin 75 mg/m\^2 by IV infusion Q3W, given on cycle day 1;Drug: Corboplatin AUC 5 by IV infusion Q3W, given on cycle day 1;Drug: Pemetrexed 500 mg/m\^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.Drug:Paclitaxel 175 mg/m\^2 by IV infusion Q3W;Drug:Docetaxel 60-75 mg/m\^2 by IV infusion Q3W

Experimental

Toripalimab DRUG

Toripalimab 240 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1;Drug: Cisplatin 75 mg/m\^2 by IV infusion Q3W, given on cycle day 1;Drug: Corboplatin AUC 5 by IV infusion Q3W, given on cycle day 1;Drug: Pemetrexed 500 mg/m\^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.Drug:Paclitaxel 175 mg/m\^2 by IV infusion Q3W;Drug:Docetaxel 60-75 mg/m\^2 by IV infusion Q3W

Also known as: Toripalimab IV 240mg + platinum-based doublet chemotherapy

Active Comparator; Experimental

Eligibility Criteria

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

You may qualify if:

• Aged 18 -75 years, regardless of gender；
• ECOG score 0-1;
• Treatment-naive, histologically confirmed resectable, stage II, IIIA, IIIB (N2) (AJCC staging system, version 8) NSCLC ;
• Measurable lesions based on the response evaluation criteria in solid tumors version 1.1;
• Tumor tissue specimens available for pathological diagnosis, detection of PD-L1 expression and biomarkers prior to randomization ;
• According to the doctor's judgment, lung function can meet the requirements of pneumonectomy;
• Confirming the absence of EGFR/ALK sensitive gene mutations through molecular pathological diagnosis of the organization;
• Good organ function:
• Bone marrow function: absolute neutrophil count ≥ 1.5 × 109/L, platelet count ≥ 80 × 109/L, hemoglobin ≥9 g/dL; Liver function: total bilirubin ≤ 1.5 × ULN, ALT and AST ≤ 1.5 × ULN; Renal function: serum creatinine ≤ 1.5 × ULN or serum creatinine clearance rate ≥ 60 mL/min; blood urea nitrogen ≤ 200mg/L;
• Having sufficient understanding of this study and being willing to sign the informed consent form; 10. For female subjects of childbearing age, the serum pregnancy test should be negative within 3 days before receiving the first dose (cycle 1, day 1).

You may not qualify if:

• Have locally advanced unresectable or metastatic disease; unresectable includes unresectable stage III non-small cell lung cancer as defined by the Multidisciplinary Diagnosis and Treatment Consensus (2019 edition), including partial stages IIIA and IIIB and all stage IIIC, N2: single station mediastinal lymph nodes with short diameter≥3cm or N2: multi-station mediastinal metastasis with lymph node fusion and the short diameter of lymph node ≥2cm on CT, T4 invading esophagus, heart, aorta, pulmonary veins and all the N3;
• NSCLC involving superior sulcus, large cell neuroendocrine carcinoma (LCNEC), sarcomatoid tumor;
• Participants with known EGFR sensitive mutations or ALK translocation, EGFR and ALK mutation status needs to be identified for the subjects with non-squamous cell carcinoma;
• Previous treatment with systemic antitumor therapy for early NSCLC, including investigational product;
• History of (non-infectious) pneumonitis/interstitial lung disease requiring steroid treatment, or ongoing pneumonitis/interstitial lung disease requiring steroid treatment;
• Active tuberculosis；
• Active infection requiring systemic treatment；
• Subjects with any known or suspected autoimmune disorder or immunodeficiency, with the following exceptions: hypothyroidism, hormone therapy is not needed, or well controlled at physiological dose; controlled type I diabetes;
• Uncontrolled active hepatitis B (defined as positive hepatitis B surface antigen \[HBsAg\] in screening period with HBV-DNA detected higher than the upper limit of normal at the clinical laboratory of the study center); (the subjects with HBV-DNA assay \<500 IU/mL within 28 days prior to randomization who have received local standard antiviral therapy for at least 14 days and are willing to receive antiviral therapy continuously during the study can be enrolled); active hepatitis C (defined as positive hepatitis C surface antibody \[HCsAb\] in screening period and positive HCV-RNA);
• Known human immunodeficiency virus (HIV) infection (known positive HIV antibody);
• Vaccination of live vaccine within 30 days prior to the first dose. Including but not limited to the following: parotitis, rubella, measles, varicella/ herpes zoster (varicella), yellow fever, Rabies, Bacille Calmette-Guérin (BCG) and typhoid vaccine (inactivated virus vaccine allowed);
• ≥ grade 2 peripheral neuropathy；
• Previous use of PD-1/PD-L1 agent or the drug acting on another targeted T cell receptor (e.g., CTLA-4, OX-40);
• Severe allergic reaction to other monoclonal antibodies;
• History of serious allergy to Pemetrexed, paclitaxel or docetaxel, cisplatin, carboplatin or its preventive medications;

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Xuwei Cai

  Department of Radiation Oncology， Shanghai Chest Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

• Zhigang Li

  Department of Thoracic Surgery， Shanghai Chest Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

• Songbing Qin

  Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuwei Cai

CONTACT

02122200000; birdhome2000@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Model Details: Parallel

Study Record Dates

• First Submitted: May 26, 2024
• First Posted: May 31, 2024
• Study Start: September 12, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)