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
- 尚未招募
- 入组人数
- 43
- 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 malignant pleural effusion or pericardial effusion;
- •No prior history of thoracic radiotherapy or thoracic surgery;
- •No prior systemic anti-tumor therapy;
- •ECOG performance status 0-2, with a life expectancy of ≥12 weeks;
- •At least one measurable lesion per RECIST 1.1 criteria;
- •No history of interstitial pneumonia;
- •No history of immune-related pneumonitis;
- •No history of autoimmune diseases;
- •No history of significant active pulmonary infection;
- •No use of corticosteroid therapy within 14 days prior to enrollment;
- •No Grade ≥3 hematologic toxicity or hepatic/renal impairment;
- •No brainstem metastases and no significant neurological symptoms;
- •For subjects with coexisting HBV/HCV infection, hepatic impairment ≤ Grade 1 after prior active antiviral therapy;
- •All subjects have provided written informed consent;
排除标准
- •Presence of interstitial pneumonia or infectious fever prior to treatment;
- •Comorbid autoimmune diseases or long-term oral corticosteroid use (including those who received oral corticosteroids within 14 days prior to treatment);
- •Prior history of thoracic radiotherapy or thoracic surgery;
- •Presence of Grade ≥3 hematologic toxicity or hepatic/renal impairment;
- •Hypersensitivity to adebrelimab;
- •Significant respiratory symptoms that preclude tolerance to radiotherapy;
- •Active hepatitis B or C infection, currently on antiviral therapy, and with liver function impairment of Grade 2 or above;
- •Presence of pleural effusion or pericardial effusion;
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: 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)
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)
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).)
研究者
Lin Xiao
Deputy Director of the Oncology Department
Jiangmen Central Hospital