Iparomlimab and Tuvonralimab Injection Combined With SBRT in Patients With Early-Stage Non-Small Cell Lung Cancer

A Single-center, Single-arm Clinical Study on the Efficacy and Safety of Iparomlimab and Tuvonralimab Injection Combined With SBRT in Patients With Early-Stage Non-Small Cell Lung Cancer

Major objectives to evaluate the efficacy and safety of lparomlimab and Tuvonralimab Injection ((QL1706, an Anti-PD-1/CTLA-4 Combined Antibody)) combined with SBRT in patients with early-stage non-small cell lung cancer.

This single-arm, single-center clinical study aims to evaluate the efficacy and safety of lparomlimab and Tuvonralimab Injection ((QL1706, an Anti-PD-1/CTLA-4 Combined Antibody)) combined with SBRT in patients with early-stage non-small cell lung cancer. This study consists of three phases: screening, treatment, and follow-up.Efficacy evaluation and safety monitoring should be performed throughout the study.

Inclusion Criteria:

• Understand and voluntarily sign the informed consent form for this study;
• Age ≥ 18 years;
• ECOG performance status of 0-1;
• Histologically confirmed non-small cell lung cancer, meeting AJCC 8th edition Stage IA-IB (tumor size ≤ 4cm, N0M0), Stage IIA (≤5cm, N0M0), or Stage IIB (>5cm and ≤7cm, N0M0);
• At least one repeatable measurable lesion at baseline (according to RECIST 1.1 criteria);
• Function of vital organs within 7 days prior to initial treatment meets the following requirements (use of any blood components or colony-stimulating factors within 14 days prior to enrollment is not allowed): Hemoglobin (Hb) ≥ 90 g/L; White Blood Cell (WBC) count ≥ 3.5 × 10^9/L; Absolute Neutrophil Count (ANC) ≥ 1.5 × 10^9/L; Platelets (PLT) ≥ 80 × 10^9/L; Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × Upper Limit of Normal (ULN); if liver metastases are present, AST and ALT ≤ 5 × ULN; Total Bilirubin (TBIL) ≤ 1.5 × ULN; Blood Urea Nitrogen (BUN) and Creatinine (Cr) ≤ 1.5 × ULN (and Creatinine Clearance (CCr) ≥ 50 mL/min); Left Ventricular Ejection Fraction (LVEF) ≥ 50%; QT interval corrected by Fridericia's formula (QTcF) < 470 milliseconds;
• Eligible patients of childbearing potential must agree to use a reliable method of contraception together with their partner during the trial period and for at least 180 days after the last dose of the study drug.

Exclusion Criteria:

• Inability to comply with the research protocol or study procedures.
• Previous receipt of any treatment, including chemotherapy or radiotherapy, for the currently diagnosed lung cancer.
• Patients with positive driver gene mutations such as EGFR, ALK, or ROS1.
• History of allergy or hypersensitivity to the investigational drug(s) or any of their excipients, or a history of atopy.
• Presence of active pulmonary tuberculosis, radiation pneumonitis, drug-induced pneumonitis, or other diseases, symptoms, or signs indicating severe pulmonary impairment during the screening period.
• Concurrent severe cardiovascular or cerebrovascular diseases.
• Receipt of broad-spectrum antibiotic therapy via any route within 30 days prior to the first dose.
• Positive anti-HIV test; positive Hepatitis B surface antigen (HBsAg) with HBV-DNA above the upper limit of normal (ULN); active Hepatitis C virus (HCV) infection.
• Evident bleeding tendency or other significant evidence of coagulation disorders.
• Current interstitial pneumonia or interstitial lung disease, or a prior history of interstitial pneumonia or interstitial lung disease requiring corticosteroid treatment; or other conditions such as pulmonary fibrosis or organizing pneumonia that may interfere with the assessment and management of immune-related pulmonary toxicity.
• Clinically symptomatic moderate or severe ascites requiring therapeutic paracentesis or drainage (except for cases with only minimal ascites visible on imaging without clinical symptoms), or uncontrolled or moderate-to-large pleural effusion or pericardial effusion.
• Ongoing systemic corticosteroid therapy or other immunosuppressive agents within 14 days prior to the first dose, or use of immunostimulants (including but not limited to interferon or interleukin-2) within 4 weeks prior.
• Diagnosis of other malignancies within 5 years prior to enrollment, except for radically resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the cervix.
• Active autoimmune disease or a history of autoimmune disease within 4 weeks prior to enrollment.
• Patients deemed by the investigator to be unsuitable for participation in this study.