Efficacy and Safety of Low-dose Thoracic Radiotherapy Followed by Adebrelimab Plus Chemotherapy and Sequential Adebrelimab Maintenance Therapy for Extensive-stage Small Cell Lung Cancer: A Prospective, Multicenter Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Progression-Free Survival（PFS）
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years and ≤75 years.
- •Histologically or cytologically confirmed SCLC.
- •No prior thoracic radiotherapy or thoracic surgery.
- •No prior systemic anti-tumor therapy.
- •ECOG performance status 0-2 and life expectancy ≥12 weeks.
- •At least one measurable lesion per RECIST 1.
- •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.
- •Essentially normal hepatic and renal function: 8.
- •Serum creatinine ≤1.5×ULN or creatinine clearance (CrCl) ≥50 mL/min; 8.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN is acceptable in patients with liver metastases); 8.
- •Total bilirubin (TBIL) ≤1.5×ULN; 8.
- •Albumin ≥30 g/L and prealbumin ≥150 g/L.
- •Urine protein ≤1+ or <1000 mg/24h.
- •All patients have provided full informed consent.
排除标准
- •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.
- •Concomitant autoimmune disease, or long-term oral corticosteroid use (including oral corticosteroids within 14 days before treatment).
- •Allergy to adebrelimab.
- •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.
- •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.
- •MRI evidence of leptomeningeal, brainstem, or spinal cord metastases, or symptomatic brain metastases (e.g., headache, nausea, vomiting, visual impairment, or visual field defects).
- •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).
- •Hypertension poorly controlled despite two antihypertensive agents (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg).
- •Poorly controlled blood glucose (defined as:
- •two consecutive fasting blood glucose values >10 mmol/L; or
- •HbA1c ≥8%), or diabetic gangrene.
- •Any deep vein thrombosis (allowed if stable on low-molecular-weight heparin or similar therapy for >2 weeks), arterial thrombosis, or pulmonary embolism.
- •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.
研究组 & 干预措施
Low-Dose Radiotherapy + EP/EC + Adebrelimab
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.
干预措施: Etoposide (Drug)
Low-Dose Radiotherapy + EP/EC + Adebrelimab
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.
干预措施: Adebrelimab (Drug)
Low-Dose Radiotherapy + EP/EC + Adebrelimab
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.
干预措施: Thoracic Radiotherapy (Radiation)
Low-Dose Radiotherapy + EP/EC + Adebrelimab
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.
干预措施: Cisplatin (Drug)
Low-Dose Radiotherapy + EP/EC + Adebrelimab
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.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Progression-Free Survival（PFS）
时间窗: From the date of first radiotherapy to the date of first documented disease progression, metastasis.
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.
次要结局
- Overall Survival (OS)(From date of first radiotherapy to date of death from any cause, assessed up to 36 months.)
- Overall Response Rate (ORR)(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)(Baseline (within 28 days prior to first dose), then every 8 weeks (±7 days) from radiotherapy initiation until 2 years post-treatment.)
- To investigate the association between distinct molecular subtypes and clinical outcomes, including prognosis and treatment-related toxicity.(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).)
- Incidence of Treatment-Emergent Adverse Events(From date of first low-dose radiotherapy to 30 days after last dose.)
研究者
Lin Xiao
Deputy Director of the Oncology Department
Jiangmen Central Hospital