Low-dose Thoracic Radiotherapy Followed by Adebrelimab Plus Chemotherapy, and Then Sequential Maintenance Therapy With Adebrelimab for Extensive-stage Small Cell Lung Cancer

Phase 2RecruitingNCT07583550

Jiangmen Central Hospital43 enrolled

Overview

This study is a multicenter, prospective investigation aiming to evaluate the efficacy and safety of low-dose radiotherapy (15Gy/1.5 Gy bid × 10 fractions) combined with 4-6 cycles of systemic chemotherapy concurrently with Adebrelimab, followed by Adebrelimab maintenance therapy for up to two years, in subjects with extensive-stage small cell lung cancer (ES-SCLC). Additionally, immunohistochemical detection of the expression levels of four key transcriptional proteins-YAP1, NEUROD1, ASCL1, and POU2F3-will be performed to guide the molecular subtyping of SCLC. Based on these findings, we will explore the differential therapeutic outcomes of this regimen across distinct molecular subtypes (A/N/P/Y/I/AN/QN), with the goal of identifying the subject population most likely to benefit from this treatment modality, thereby optimizing clinical decision-making.

This study plans to prospectively enroll 43 subjects with extensive-stage small cell lung cancer (ES-SCLC) without malignant pleural effusion from multiple centers. All subjects will first receive low-dose radiotherapy (DT 15 Gy, 1.5 Gy/fraction × 10 fractions, BID). Within one week after radiotherapy completion, subjects will receive 4-6 cycles of systemic chemotherapy (EP or EC regimen) combined with adebrelimab (anti-PD-L1 antibody), followed by adebrelimab maintenance therapy for two years. Through this regimen, we aim to achieve survival outcomes comparable to or even superior to those of the MATCH study from West China Hospital (median PFS 6.9 months, median OS 16.9 months) and the NCT04562337 study from Shandong Cancer Hospital (median PFS 10.1 months, median OS 21.4 months), with manageable toxicity profiles. Additionally, immunohistochemistry (IHC) will be performed to detect the expression levels of four key transcriptional proteins-YAP1, NEUROD1, ASCL1, and POU2F3-which are used to guide the molecular subtyping of small cell lung cancer. Based on these results, we will investigate the differential efficacy of this treatment regimen across distinct molecular subtypes (A/N/P/Y/I/AN/QN), with the goal of identifying the subject population most likely to benefit from this approach and ultimately better serving clinical practice.

Study Type

INTERVENTIONAL

Allocation

Purpose

Interventions

EtoposideDRUG

Etoposide 100 mg/m² on days 1-3 plus cisplatin 25 mg/m² on days 1-3, every 3 weeks (q3w), or etoposide 100 mg/m² on days 1-3 plus carboplatin AUC 5 on day 1, every 3 weeks (q3w).

CisplatinDRUG

Etoposide (100 mg/m²) and cisplatin (25 mg/m²) were administered on days 1-3 of each 3-week cycle.

CarboplatinDRUG

Etoposide (100 mg/m²) was given on days 1-3 and carboplatin (AUC 5) on day 1 of each 3-week cycle.

AdebrelimabDRUG

20 mg/kg intravenously on day 1, repeated every 21 days (q3w). Administered concurrently with chemotherapy for 4-6 cycles, followed by maintenance monotherapy for up to 2 years.

Thoracic RadiotherapyRADIATION

All subjects will first receive low-dose radiotherapy (DT 15 Gy, 1.5 Gy per fraction × 10 fractions, BID). Within one week after radiotherapy completion, they will receive 4-6 cycles of systemic chemotherapy (EP or EC regimen) combined concurrently with adebrelimab. Following the 4-6 cycles of chemo-immunotherapy, adebrelimab maintenance therapy will be continued for two years.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥18 years and ≤75 years. 2. Histologically or cytologically confirmed SCLC. 3. No prior thoracic radiotherapy or thoracic surgery. 4. No prior systemic anti-tumor therapy. 5. ECOG performance status 0-2 and life expectancy ≥12 weeks. 6. At least one measurable lesion per RECIST 1.1. 7. Adequate bone marrow function to tolerate anti-tumor therapy: WBC ≥3×10⁹/L, Hb ≥80 g/L, PLT ≥75×10⁹/L, and absolute neutrophil count (NEUT) ≥1.5×10⁹/L. 8. Essentially normal hepatic and renal function: 8.1. Serum creatinine ≤1.5×ULN or creatinine clearance (CrCl) ≥50 mL/min; 8.2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN is acceptable in patients with liver metastases); 8.3. Total bilirubin (TBIL) ≤1.5×ULN; 8.4. Albumin ≥30 g/L and prealbumin ≥150 g/L. 9. Urine protein ≤1+ or \<1000 mg/24h. 10. All patients have provided full informed consent. Exclusion Criteria: 1. Pre-existing interstitial lung disease (with or without clinical symptoms) or uncontrolled infectious pneumonia (e.g., accompanied by cough, fever \>38°C, dyspnea, tachypnea, etc.) prior to treatment. 2. Concomitant autoimmune disease, or long-term oral corticosteroid use (including oral corticosteroids within 14 days before treatment). 3. Allergy to adebrelimab. 4. Positive HIV antibody, active hepatitis B (HBV-DNA \>10³ IU/mL), active hepatitis C (HCV-RNA above the lower limit of detection of the study site), active pulmonary tuberculosis (defined as: fever, night sweats, chest pain, etc.; or acid-fast bacilli found in sputum or bronchoalveolar lavage fluid; or chest CT showing active signs such as patchy infiltrates or cavities), or positive syphilis antibody. 5. Moderate or large pleural effusion (maximum depth \>3 cm on chest ultrasound or CT, estimated volume \>500 mL) or moderate or large pericardial effusion (maximum diastolic width \>1 cm on echocardiography, estimated volume \>100 mL), or poorly controlled pleural/pericardial effusion (defined as requiring ≥2 drainage procedures within 1 month). Patients may be enrolled if effusion becomes minimal or undetectable after drainage. 6. MRI evidence of leptomeningeal, brainstem, or spinal cord metastases, or symptomatic brain metastases (e.g., headache, nausea, vomiting, visual impairment, or visual field defects). 7. Severe cardiac or cerebrovascular disease, including: New York Heart Association (NYHA) class ≥2 heart failure; acute coronary syndrome (e.g., myocardial infarction, unstable angina) within 6 months before enrollment; frequent and uncontrolled arrhythmias (excluding transient atrial fibrillation/flutter) despite antiarrhythmic therapy for ≥2 weeks; acute cerebrovascular events (e.g., transient ischemic attack, cerebral infarction, cerebral hemorrhage). 8. Hypertension poorly controlled despite two antihypertensive agents (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg). 9. Poorly controlled blood glucose (defined as: 1. two consecutive fasting blood glucose values \>10 mmol/L; or 2. HbA1c ≥8%), or diabetic gangrene. 10. Any deep vein thrombosis (allowed if stable on low-molecular-weight heparin or similar therapy for \>2 weeks), arterial thrombosis, or pulmonary embolism. 11. Pregnant or lactating women, or women of childbearing potential who are unwilling to use effective contraception during the study and for at least 6 months after the last dose.

Outcomes

Primary Outcomes

Progression-Free Survival（PFS）

Progression-free survival (PFS), defined as the time from the initiation of radiotherapy to the first documented disease recurrence/progression, metastasis, or death from any cause.

Time frame: From the date of first radiotherapy to the date of first documented disease progression, metastasis.

Secondary Outcomes

Overall Survival (OS)

Overall survival (OS), defined as the time from the initiation of radiotherapy to death from any cause.

Time frame: From date of first radiotherapy to date of death from any cause, assessed up to 36 months.

Overall Response Rate (ORR)

The objective response rate (ORR), defined as the proportion of subjects achieving complete response (CR) or partial response (PR) per RECIST 1.1 criteria based on evaluable lesions in the lungs and distant metastases (including primary tumor, lymph nodes, and distant metastatic lesions), relative to the total enrolled population.

Time frame: Baseline (within 28 days prior to first dose), then every 8 weeks (±7 days) from radiotherapy initiation until 2 years post-treatment.

Disease Control Rate (DCR)

The disease control rate (DCR), defined as the proportion of subjects achieving complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1 criteria based on evaluable lesions in the lungs and distant metastases (including primary tumor, lymph nodes, and distant metastatic lesions), relative to the total enrolled population.

Time frame: Baseline (within 28 days prior to first dose), then every 8 weeks (±7 days) from radiotherapy initiation until 2 years post-treatment.

Incidence of Treatment-Emergent Adverse Events

Frequency, severity, and relationship of adverse events assessed by CTCAE v5.0.

Time frame: From date of first low-dose radiotherapy to 30 days after last dose.

To investigate the association between distinct molecular subtypes and clinical outcomes, including prognosis and treatment-related toxicity.

Immunohistochemistry (IHC) for YAP1, NEUROD1, ASCL1, and POU2F3 to determine molecular subtypes; prognosis assessed via Kaplan-Meier and Cox regression; toxicity graded per CTCAE v5.0.

Time frame: Baseline: collect tumor tissue (archived FFPE or fresh biopsy) prior to treatment initiation; prognosis follow-up until progression or death (imaging q6w, survival q3m); toxicity monitoring until 30 days post-last dose (recorded at each visit).