Lung, Radiotherapy
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGEtoposide
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).
DRUGCisplatin
Etoposide (100 mg/m²) and cisplatin (25 mg/m²) were administered on days 1-3 of each 3-week cycle.
DRUGCarboplatin
Etoposide (100 mg/m²) was given on days 1-3 and carboplatin (AUC 5) on day 1 of each 3-week cycle.
DRUGAdebrelimab
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.
RADIATIONThoracic Radiotherapy
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.
Sponsors
Jiangmen Central Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years and ≤75 years; 2. Histologically or cytologically confirmed SCLC; 3. No malignant pleural effusion or pericardial effusion; 4. No prior history of thoracic radiotherapy or thoracic surgery; 5. No prior systemic anti-tumor therapy; 6. ECOG performance status 0-2, with a life expectancy of ≥12 weeks; 7. At least one measurable lesion per RECIST 1.1 criteria; 8. No history of interstitial pneumonia; 9. No history of immune-related pneumonitis; 10. No history of autoimmune diseases; 11. No history of significant active pulmonary infection; 12. No use of corticosteroid therapy within 14 days prior to enrollment; 13. No Grade ≥3 hematologic toxicity or hepatic/renal impairment; 14. No brainstem metastases and no significant neurological symptoms; 15. For subjects with coexisting HBV/HCV infection, hepatic impairment ≤ Grade 1 after prior active antiviral therapy; 16. All subjects have provided written informed consent;
Exclusion criteria
1. Presence of interstitial pneumonia or infectious fever prior to treatment; 2. Comorbid autoimmune diseases or long-term oral corticosteroid use (including those who received oral corticosteroids within 14 days prior to treatment); 3. Prior history of thoracic radiotherapy or thoracic surgery; 4. Presence of Grade ≥3 hematologic toxicity or hepatic/renal impairment; 5. Hypersensitivity to adebrelimab; 6. Significant respiratory symptoms that preclude tolerance to radiotherapy; 7. Active hepatitis B or C infection, currently on antiviral therapy, and with liver function impairment of Grade 2 or above; 8. Presence of pleural effusion or pericardial effusion;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival（PFS） | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From date of first radiotherapy to date of death from any cause, assessed up to 36 months. | Overall survival (OS), defined as the time from the initiation of radiotherapy to death from any cause. |
| 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. | 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. |
| 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. | 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. |
| Incidence of Treatment-Emergent Adverse Events | From date of first low-dose radiotherapy to 30 days after last dose. | Frequency, severity, and relationship of adverse events assessed by CTCAE v5.0. |
| 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). | 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. |
Outcome results
None listed