A Multicenter, Open-label, Randomized, Prospective Clinical Study of Adebrelimab Consolidation Therapy for Limited-Stage Small-Cell Lung Cancer (LS-SCLC) Without Progression After Concurrent Chemoradiotherapy

A Multicenter, Open-label, Randomized, Prospective Clinical Study of Adebrelimab Consolidation Therapy for Limited-Stage Small-Cell Lung Cancer (LS-SCLC) Without Progression After Concurrent Chemoradiotherapy

This study aims to evaluate the efficacy and safety of adebrelimab consolidation therapy after progression-free response of concurrent chemoradiotherapy in patients with limited-stage small cell lung cancer. This study plans to enroll patients with untreated limited-stage small cell lung cancer who meet the inclusion criteria. The eligible patients will be randomly divided 1:1 into two groups to receive treatment regimens for residual lymph nodes and involved irradiated areas. That is, carboplatin AUC 5, D1 + etoposide 100 mg/m…^2 on days 1, 2, and 3 + thoracic radiotherapy (residual lymph nodes or involved irradiated areas), with each 3-week cycle. After 4 cycles of concurrent chemoradiotherapy, the non-progressing subjects will continue to receive adebrelimab (1200 mg, IV, Q3W) maintenance therapy.

Inclusion Criteria:

1.Age ≥ 18 and ≤ 75 years, regardless of gender. 2.Histopathologically confirmed, untreated limited-stage small cell lung cancer (LS-SCLC) (stage I-III per AJCC 8th edition, with all lesions encompassed in a tolerable radiation plan).

3.Clinically staged T1-2N0, operable LS-SCLC patients who are ineligible for surgery or refuse surgery.

4.ECOG performance status 0-1. 5.Expected survival ≥ 3 months. 6.At least one measurable lesion per RECIST 1.1. 7.Pulmonary function: FEV1 > 70% of predicted value. 8.Adequate hematologic and end-organ function, with laboratory results obtained within 7 days before first study treatment:

1. Hematology: Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L without G-CSF support within 14 days before first treatment; lymphocyte count (LC) ≥ 0.5×10⁹/L; platelet count (PLT) ≥ 90×10⁹/L without transfusion, G-CSF, or other hematopoietic stimulants within 14 days before first treatment.
2. Hepatic function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN; total bilirubin (TBIL) ≤ 1.5 × ULN (≤3.0 mg/dL for patients with confirmed Gilbert syndrome).
3. Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 50 mL/min (calculated by Cockcroft-Gault, CKD-EPI, or MDRD equation); urine protein < 2+ (if urine protein ≥ 2+, 24-hour urine protein must be < 1 g for eligibility).
4. Coagulation: International normalized ratio (INR) ≤ 1.5; activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
5. Echocardiography: Left ventricular ejection fraction (LVEF) ≥ 50%. 9.Sexually active subjects of reproductive potential (non-sterilized) must agree to use at least one medically accepted contraceptive method during study treatment and for 6 months after treatment completion. For females of reproductive potential: serum pregnancy test (HCG) must be negative within 7 days before first dosing.

10.Subjects are voluntarily enrolled, provide written informed consent, have good compliance, and agree to follow-up.

Exclusion Criteria:

1. Histologically confirmed combined small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC).

2. Prior systemic anti-tumor therapy or immune checkpoint inhibitor therapy for SCLC.

3. Extensive-stage SCLC.

4. Presence of malignant pleural effusion. If aspiratable pleural effusion is present during screening, at least one thoracentesis must be performed to confirm the presence or absence of malignant cells.

5. Subjects with known or suspected interstitial lung disease (ILD); other moderate-to-severe pulmonary diseases that may interfere with the detection or management of drug-related pulmonary toxicity and severely impair respiratory function, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/bronchiolitis obliterans, etc.

6. History of active, known or suspected autoimmune disease, including but not limited to myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, etc.

   (Exceptions: Type 1 diabetes mellitus (glycemic control with insulin); residual hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement therapy; conditions not expected to relapse in the absence of external trigger.

   Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo only (excluding psoriatic arthritis) may be enrolled if: rash involves <10% of body surface area; disease is well controlled at baseline with only low-potency topical steroids; and no acute exacerbation in the past 12 months (no PUVA, methotrexate, retinoids, biologics, oral calcineurin inhibitors, high-potency or oral steroids).)

7. Concomitant malignancy diagnosed ≤3 years before first study treatment, except adequately treated papillary thyroid carcinoma, cervical carcinoma in situ, basal or squamous cell skin cancer, locally controlled prostate cancer after radical surgery, ductal carcinoma in situ after radical surgery (hormonal therapy for non-metastatic prostate or breast cancer is allowed).

8. History of clinically significant cardiovascular disease, including but not limited to:

   Congestive heart failure (NYHA class >2); Unstable angina; Myocardial infarction within 3 months before signing ICF; Any severe supraventricular or ventricular arrhythmia requiring treatment or intervention.

9. Severe infection within 4 weeks before first treatment, including but not limited to bacteremia requiring hospitalization, severe pneumonia, etc.; active infection of CTCAE grade ≥2 requiring systemic antibiotics within 2 weeks before first treatment.

10. Active tuberculosis within 1 year before enrollment by history or CT scan, or history of active tuberculosis >1 year ago without standard treatment.

11. History of immunodeficiency, including positive HIV serology.

12. Active hepatitis B or hepatitis C.(HBsAg-positive or HBcAb-positive subjects may be enrolled if HBV DNA < upper limit of normal (ULN) of the local laboratory (if no ULN, HBV DNA <1000 copies/mL or 500 IU/mL); HCV Ab-positive subjects may be enrolled if HCV RNA < ULN of the local laboratory (if no ULN, HCV RNA <500 IU/mL).)

13. Receipt of systemic immunosuppressive therapy within 14 days before first treatment, including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents.

(1)Patients receiving short-term systemic immunosuppression (e.g., corticosteroids for management/prophylaxis of nausea, vomiting, or hypersensitivity) may be enrolled at the investigator's discretion; a washout period before randomization may be required.

(2)Allowed: inhaled corticosteroids for COPD; mineralocorticoids (e.g., fludrocortisone) for orthostatic hypotension; low-dose corticosteroid replacement (≤10 mg/day prednisone or equivalent) for adrenal insufficiency.

14.Major surgery within 28 days before first treatment (except diagnostic surgery), or expected major surgery during the study (except diagnostic surgery).

15.Administration of live attenuated vaccine within 28 days before first treatment, or anticipated need during the study (live attenuated influenza vaccine is prohibited within 28 days before first treatment, during treatment, and for 5 months after the last dose of adebrelimab).

16.Prior allogeneic bone marrow transplant or solid organ transplant. 17.History of severe hypersensitivity to monoclonal antibody/fusion protein drugs.

18.Known psychiatric disorder, alcoholism, drug abuse or substance abuse. 19.Any other condition that, in the investigator's judgment, may prematurely terminate the study, e.g., poor protocol compliance, other severe diseases requiring concurrent treatment, significant laboratory abnormalities, or family/social factors affecting subject safety or data/sample collection.