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

20 de julio de 2026 actualizado por: Lin Xiao, Jiangmen Central Hospital

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

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.

Descripción general del estudio

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

43

Fase

  • Fase 2

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

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;

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: 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.
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.
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).
Etoposide (100 mg/m²) and cisplatin (25 mg/m²) were administered on days 1-3 of each 3-week cycle.
Etoposide (100 mg/m²) was given on days 1-3 and carboplatin (AUC 5) on day 1 of each 3-week cycle.
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.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Progression-Free Survival(PFS)
Periodo de tiempo: 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.
From the date of first radiotherapy to the date of first documented disease progression, metastasis.

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Incidence of Treatment-Emergent Adverse Events
Periodo de tiempo: 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.
From date of first low-dose radiotherapy to 30 days after last dose.
Overall Survival (OS)
Periodo de tiempo: 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.
From date of first radiotherapy to date of death from any cause, assessed up to 36 months.
Overall Response Rate (ORR)
Periodo de tiempo: 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.
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)
Periodo de tiempo: 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.
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.
Periodo de tiempo: 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.
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).

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Estimado)

21 de julio de 2026

Finalización primaria (Estimado)

30 de octubre de 2027

Finalización del estudio (Estimado)

1 de enero de 2028

Fechas de registro del estudio

Enviado por primera vez

21 de abril de 2026

Primero enviado que cumplió con los criterios de control de calidad

6 de mayo de 2026

Publicado por primera vez (Actual)

13 de mayo de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

22 de julio de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

20 de julio de 2026

Última verificación

1 de julio de 2026

Más información

Términos relacionados con este estudio

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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