The Effect of Toripalimab Plus Radiotherapy in Patients With Operable Stage II-IIIA (N+) Non Small Cell Lung Cancer

NCT ID: NCT05798845

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-20
• Study Completion Date: 2026-12-31

Brief Summary

This randomized phase II trial is to explore the clinical efficacy, safety and feasibility of neoadjuvant immunotherapy plus radiotherapy compared with neoadjuvant immunotherapy plus chemotherapy in operable stage II-IIIA (N+) non small cell lung cancer (NSCLC) and the optimal radiotherapy pattern.

Detailed Description

In recent years, the survival rate after diagnosis of non small cell lung cancer (NSCLC) has improved with advances in treatment. In terms of 5-year average overall survival (OS) by stage at the time of diagnosis, OS decreases significantly from stage IB to IIIA NSCLC, with 68% for stage IB, 53-60% for stage II, and 36% for stage IIIA. How to optimize the perioperative treatment strategy to reduce postoperative recurrence and prolong the survival of patients has raised great concern in early and mid-stage NSCLC. Radiotherapy combined with immunotherapy is suggested for advanced NSCLC in preclinical basic studies and recent clinical trials. Stereotactic body radiation therapy (SBRT) at 8 Gy × 3 Fx plays an effective immunoregulated role and can further enhance the antitumor immune response promoted by immune checkpoint inhibitors (ICIs). Although little is known about the optimal SBRT dose and fraction pattern, 6 Gy × 5 Fx or 8-9 Gy × 3 Fx have shown effectiveness in clinical studies.

Conditions

NSCLC

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Radiation: primary tumor SBRT, DT: 24Gy/3Fx, d1-3; positive lymph nodes LDRT, DT: 2Gy/2Fx, d1-2, d22-23 (2 cycles) ; Drug: toripalimab 240mg ivgtt d4, d24 (2 cycles)

Group Type: EXPERIMENTAL

SBRT+LDRT

Intervention Type: RADIATION

primary tumor SBRT, DT: 24Gy/3Fx, d1-3; positive lymph nodes LDRT, DT: 2Gy/2Fx, d1-2, d22-23 (2 cycles)

Toripalimab

Intervention Type: DRUG

toripalimab 240mg ivgtt d4, d24 (2 cycles)

Arm B

Drug: Chemotherapy + toripalimab 240mg ivgtt d1, d22 (2 cycles)

Chemotherapy regimen:

Non-squamous carcinoma: pemetrexed + platinum or paclitaxel + platinum. Squamous carcinoma: paclitaxel + platinum or gemcitabine + platinum

Group Type: ACTIVE_COMPARATOR

Chemotherapy drug

Intervention Type: DRUG

Non-squamous carcinoma: pemetrexed + platinum or paclitaxel + platinum Squamous carcinoma: paclitaxel + platinum or gemcitabine + platinum

Toripalimab

Intervention Type: DRUG

toripalimab 240mg ivgtt d1, d22 (2 cycles)

Interventions

SBRT+LDRT

primary tumor SBRT, DT: 24Gy/3Fx, d1-3; positive lymph nodes LDRT, DT: 2Gy/2Fx, d1-2, d22-23 (2 cycles)

Intervention Type: RADIATION

Toripalimab

toripalimab 240mg ivgtt d4, d24 (2 cycles)

Intervention Type: DRUG

Chemotherapy drug

Non-squamous carcinoma: pemetrexed + platinum or paclitaxel + platinum Squamous carcinoma: paclitaxel + platinum or gemcitabine + platinum

Intervention Type: DRUG

Toripalimab

toripalimab 240mg ivgtt d1, d22 (2 cycles)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 18 to 75 years old, gender is not limited.

2. ECOG performance status 0-1.

3. non-small cell lung cancer diagnosed by pathology.

4. sufficient tumor tissue available for biomarker analysis.

5. clinical staging of cT1-2N1-2M0 or T3N1M0, stage II-IIIA (8th UICC staging criteria).

6. Patients with distant metastases ruled out by CT or PET/CT and physically assessed as acceptable for radical lung cancer surgery.

7. histomolecular pathology confirming the absence of classic driver oncogene mutations in EGFR, ALK, or ROS1.

8. Basic normal function of all organs (laboratory test results within 1 week prior to enrollment).

• Bone marrow function: absolute neutrophil count (ANC) ≥ 1.5x109 /L, platelet count ≥ 100x109 /L, hemoglobin ≥ 9g/dL.
• Liver: serum total bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 2.5 times the upper limit of normal.
• Kidney: blood creatinine level ≤ 1.5 times the upper limit of normal or creatinine clearance ≥ 60 ml/min and urea nitrogen ≤ 200 mg/L.
• Urine protein <+, if urine protein + then total 24 hour protein must be <500mg.
• Blood glucose: within normal range and/or with diabetic patients on treatment but with stable blood glucose control.
• Pulmonary function: baseline FEV1 of at least 2L; if baseline FEV1 < 2L then FEV1 > 800ml is expected after surgery as assessed by a surgical specialist.
• Cardiac function: no myocardial infarction within 1 year; no unstable angina; no symptomatic severe arrhythmia; no cardiac insufficiency.

9. Voluntarily participated in this study and signed the informed consent form by himself or his agent

Exclusion Criteria

1. Pathology suggestive of compound small cell lung cancer, etc.

2. History of previous lobectomy, radiotherapy or chemotherapy.

3. Those with concurrent second primary carcinoma and a history of previous malignancy of less than 5 years (except for completely cured cervical carcinoma in situ or basal cell or squamous epithelial cell skin cancer).

4. Patients with any active autoimmune disease or a history of autoimmune disease (e.g., interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, etc.).

5. Have an active infection requiring systemic treatment or a history of active tuberculosis.

6. Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment.

7. Those with known presence or coexistence of other uncontrollable diseases that are not amenable to surgical treatment

8. Physical examination or clinical trial finds that, in the opinion of the investigator, may interfere with the results or place the patient at increased risk for treatment complications

9. Prior interstitial lung disease, drug-induced interstitial disease or any clinically evident active interstitial lung disease with idiopathic pulmonary fibrosis on baseline CT scan; uncontrolled massive pleural or pericardial effusion

10. Unstable systemic concomitant disease (active infection, moderate to severe chronic obstructive pulmonary disease, poorly controlled hypertensive disease, unstable angina pectoris, congestive heart failure, myocardial infarction occurring within 6 months, severe mental disorder requiring medication for control, liver, renal or other metabolic disease, neuropsychiatric pathology such as Alzheimer's disease)

11. History of congenital or acquired immunodeficiency disorders or organ transplantation

12. Received any of the following treatments:

• Prior radiotherapy, treatment with anti PD-1, anti PD-L1 or anti PD-L2 drugs, or other drugs that synergistically inhibit T-cell receptors such as CTLA-4, OX-40, CD137.
• Having received any investigational drug within 4 weeks
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up
• Persons who have received an antineoplastic vaccine or who have received a live vaccine within 4 weeks
• Have undergone major surgery or had severe trauma within 4 weeks

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Junshi Bioscience Co., Ltd.

OTHER

Sponsor Role: collaborator

Shanghai Chest Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiaolong Fu

director,department of radiation oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiaolong Fu, MD

Role: CONTACT

xlfu1964@126.com

862122200000 ext. 3202

Wen Feng, MD

Role: CONTACT

fengwen412@126.com

862122200000 ext. 3203

Facility Contacts

Xiaolong Fu, MD

Role: primary

021-22200000 ext. 3202

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Other Identifiers

neoRT-Lung

Identifier Type: -

Identifier Source: org_study_id