Neoadjuvant therapy for resectable stage II-III lung cancer

Neoadjuvant Therapy of SBRT Sequencial With Toripalimab and Chemotherapy in Resectable Stage II-III NSCLC Patients: A Multicenter, Openlabel, Randomized, Phase III Trial

This study is testing if adding a type of radiation therapy to an immunotherapy drug and chemotherapy can help people with early-stage lung cancer have better surgery results.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 478 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Chest Hospital (Academic / other)
• Drugs / interventions: Toripalimab, chemotherapy, radiation
• Locations: 1 site (Shanghai)
• Trial ID: NCT06437977 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of combining stereotactic body radiation therapy (SBRT) with the immunotherapy drug Toripalimab and chemotherapy in patients with resectable stage II-III non-small cell lung cancer (NSCLC). Participants are randomly assigned to receive either the combination of SBRT, Toripalimab, and chemotherapy or just Toripalimab and chemotherapy. The study aims to determine if the addition of SBRT improves surgical outcomes and overall efficacy. Patients will undergo evaluations after treatment to assess their eligibility for surgery based on established criteria.

Who should consider this trial

Good fit: Ideal candidates are treatment-naive adults aged 18-75 with histologically confirmed resectable stage II-III NSCLC and good organ function.

Not a fit: Patients with EGFR/ALK sensitive gene mutations or those with significant comorbidities affecting lung function may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve surgical outcomes and overall survival rates for patients with resectable stage II-III NSCLC.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and chemotherapy, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Aged 18 -75 years, regardless of gender；
2. ECOG score 0-1;
3. Treatment-naive, histologically confirmed resectable, stage II, IIIA, IIIB (N2) (AJCC staging system, version 8) NSCLC ;
4. Measurable lesions based on the response evaluation criteria in solid tumors version 1.1;
5. Tumor tissue specimens available for pathological diagnosis, detection of PD-L1 expression and biomarkers prior to randomization ;
6. According to the doctor's judgment, lung function can meet the requirements of pneumonectomy;
7. Confirming the absence of EGFR/ALK sensitive gene mutations through molecular pathological diagnosis of the organization;
8. 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;
9. 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).

Exclusion Criteria:

1. 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;
2. NSCLC involving superior sulcus, large cell neuroendocrine carcinoma (LCNEC), sarcomatoid tumor;
3. 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;
4. Previous treatment with systemic antitumor therapy for early NSCLC, including investigational product;
5. History of (non-infectious) pneumonitis/interstitial lung disease requiring steroid treatment, or ongoing pneumonitis/interstitial lung disease requiring steroid treatment;
6. Active tuberculosis；
7. Active infection requiring systemic treatment；
8. 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;
9. 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);
10. Known human immunodeficiency virus (HIV) infection (known positive HIV antibody);
11. 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);
12. ≥ grade 2 peripheral neuropathy；
13. Previous use of PD-1/PD-L1 agent or the drug acting on another targeted T cell receptor (e.g., CTLA-4, OX-40);
14. Severe allergic reaction to other monoclonal antibodies;
15. History of serious allergy to Pemetrexed, paclitaxel or docetaxel, cisplatin, carboplatin or its preventive medications;
16. Known serious or uncontrolled pre-existing diseases; including but not limited to cardiovascular events with hemodynamic instability, symptomatic cerebrovascular events, and hepatic cirrhosis above Child-Pugh A within 6 months;
17. History or current evidence of any disease, therapy or abnormal laboratory examination that may confuse the study results, interfere with subject's participation in the full course of the study or not meet the best interest of subject's participation in the study, as judged by investigators;
18. Other malignant tumors within 5 years prior to the first dose, except non-small cell lung cancer. The malignant tumors with negligible risk of metastasis or death (e.g., expected disease-free survival \> 5 years) and expected to achieve radical outcomes after treatment (e.g., sufficiently treated carcinoma in situ of cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated for radical surgery) can be excluded.

Where this trial is running

Shanghai

• Shanghai Chest Hospital — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Xuwei Cai — Department of Radiation Oncology， Shanghai Chest Hospital, Shanghai, China
• Study coordinator: Xuwei Cai

Conditions Stage II-III Non-small Cell Lung Cancer