Low-Dose Radiotherapy Plus Adebrelimab and Chemotherapy for Extensive-Stage Small Cell Lung Cancer
A Single-arm, Single-center, Phase II Clinical Study of Low-dose Radiotherapy Combined With Adebrelimab and Chemotherapy as First-line Treatment for Extensive-stage Small Cell Lung Cancer
This is a phase II study evaluating a novel combination therapy for untreated extensive-stage small cell lung cancer. The treatment involves an initial induction phase with the drug Adebrelimab plus standard chemotherapy and low-dose radiotherapy, followed by an Adebrelimab maintenance phase. The primary objective is to assess the efficacy of this approach in prolonging overall survival (OS) and to evaluate its safety in approximately 25 patients.
Study Overview
Status
Intervention / Treatment
Detailed Description
This is an exploratory Phase II clinical trial for previously untreated extensive-stage small cell lung cancer (ES-SCLC). The study evaluates a two-phase treatment strategy: patients first receive induction therapy with Adebrelimab combined with standard chemotherapy (EC or EP regimen) and concurrent low-dose radiotherapy (5 Gy × 5 fractions); patients achieving disease control then proceed to the maintenance phase with Adebrelimab for up to 2 years. The primary objective is to assess the regimen's efficacy in prolonging overall survival (OS). Secondary objectives include evaluating progression-free survival (PFS), objective response rate (ORR), and safety. The study plans to enroll approximately 25 patients.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Ningbo Liu
- Phone Number: +8615602036608
- Email: liuningbo@tjmuch.com
Study Locations
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Tianjin Municipality
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Tianjin, Tianjin Municipality, China, 300000
- Tianjin Medical University Cancer Institute and Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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1.Patients with pathologically confirmed extensive-stage small cell lung cancer (ES-SCLC) according to VALG staging.
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2. No prior systemic therapy for extensive-stage small cell lung cancer.
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3. Presence of measurable lesions as defined by RECIST 1.1. A previously irradiated lesion may be considered measurable only if clear progression occurs after radiotherapy and this previously irradiated lesion is not the only lesion.
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4. Aged 18-75 years.
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5. ECOG performance status: 0-2.
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6. Expected survival ≥3 months.
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7. Adequate hematological and organ function, i.e., meeting the following criteria:
a) Hematology (no blood transfusion or blood products and no use of G-CSF or other hematopoietic growth factors for correction within 14 days): i. Absolute neutrophil count (ANC) ≥1.5×10^9/L (1,500/mm^3); ii. Platelet count (PLT) ≥100×10^9/L (100,000/mm^3); iii. Hemoglobin (HB) ≥80 g/L. b) Renal: i. Calculated creatinine clearance (CrCl) ≥50 mL/min; ii. Urine protein <2+ or 24-hour urine protein <1.0 g. c) Hepatic: i. Serum total bilirubin (TBil) ≤1.5×ULN; ii. AST and ALT ≤2.5×ULN; iii. Serum albumin (ALB) ≥28 g/L. d) Coagulation: i. International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5×ULN.
e) Cardiac: i. Left ventricular ejection fraction (LVEF) ≥50%.
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8. Female patients must meet one of the following conditions:
- Menopause (defined as no menstruation for at least 1 year and no other confirmed cause other than menopause); or
- Surgical sterilization (oophorectomy and/or hysterectomy); or
- Fertile but must meet:
i. Serum pregnancy test within 3 days before drug administration must be negative; ii. Agree to use contraceptive measures with an annual failure rate <1% (from signing the ICF until at least 6 months after the last dose of the study drug); iii. Must not breastfeed.
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9. Male patients must take contraceptive measures as follows: when the partner is a woman of childbearing potential or the partner is pregnant, the male patient must remain abstinent or use a condom during the study treatment period and for at least 6 months after the last dose of the study drug to prevent embryonic exposure to the drug.
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10. Participants voluntarily agree to participate in this study, sign the informed consent form (ICF), have good compliance, and are willing to cooperate with follow-up.
Exclusion Criteria:
- 1. Patients with symptomatic brain metastases. Patients may be enrolled if symptoms remain clinically stable for at least 1 month after treatment of brain metastasis lesions and no steroids or anticonvulsants have been used for at least 1 month before study entry.
- 2. Patients who have previously received thoracic radiotherapy for limited-stage SCLC.
- 3. Prior use of anti-angiogenic drugs such as anlotinib, apatinib, and bevacizumab, or related immunotherapy drugs targeting PD-1, PD-L1, etc.
- 4. Factors affecting oral medication (e.g., inability to swallow, post-gastrointestinal resection, chronic diarrhea, and intestinal obstruction, etc.).
- 5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- 6. Imaging shows that the tumor has invaded the periphery of major blood vessels, or the investigator judges that during the subsequent study period the tumor is highly likely to invade major blood vessels and cause fatal massive bleeding.
- 7. History of severe bleeding tendency or coagulation dysfunction, including but not limited to: clinically significant hemoptysis within 3 months before enrollment (>1 tablespoon per day); or clinically significant bleeding symptoms or bleeding tendency within 4 weeks before grouping, such as gastrointestinal bleeding, bleeding gastric ulcer (including gastrointestinal perforation and/or fistula; however, patients with gastrointestinal perforation or fistula that has been surgically resected may be allowed to enroll), unhealed wounds, ulcers, or fractures, etc.
- 8. Major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days before grouping.
- 9. Arterial/venous thrombotic events within 6 months before grouping, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, and pulmonary embolism.
- 10.Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years before the first dose.
- 11.Other conditions that increase the risk of participating in the study or are related to the study drug and, according to the investigator's judgment, may make the patient unsuitable for inclusion in the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Experimental Group
Patients receive Adebrelimab (1200 mg IV Q3W) combined with standard chemotherapy (EC or EP regimen) for 4 induction cycles. Concurrent low-dose radiotherapy (5 Gy per fraction for 5 fractions) is administered during Cycle 1 or Cycle 2. Following induction, patients without disease progression (non-PD) continue to receive Adebrelimab (1200 mg IV Q3W) as maintenance therapy for up to 2 years, or until disease progression, unacceptable toxicity, or withdrawal of consent. |
Participants receive a two-phase treatment regimen. Induction (4 fixed cycles, q3w): Adebrelimab (1200 mg IV over 60 minutes, Day 1) followed by investigator's choice of standard platinum-etoposide chemotherapy (EC regimen: Carboplatin AUC=5 on Day 1 + Etoposide 100 mg/m² on Days 1-3; or EP regimen: Cisplatin 75 mg/m² on Day 1 + Etoposide 100 mg/m² on Days 1-3). Concurrent hypofractionated radiotherapy to the primary lung lesion (5 Gy per fraction for 5 fractions) is administered during Cycle 1 or Cycle 2. Maintenance: Patients without disease progression after 4 cycles continue Adebrelimab (1200 mg IV, q3w) for up to 2 years, until disease progression (per RECIST v1.1), unacceptable grade ≥3 immune-related toxicity, or withdrawal of consent. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Overall Survival (OS)
Time Frame: From enrollment until death from any cause, assessed up to approximately 24 months.
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OS is defined as the time from enrollment to death from any cause. |
From enrollment until death from any cause, assessed up to approximately 24 months.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Progression-Free Survival (PFS)
Time Frame: From enrollment until disease progression or death, assessed up to approximately 24 months.
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PFS is defined as the time from enrollment to objective tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first. |
From enrollment until disease progression or death, assessed up to approximately 24 months.
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Objective Response Rate (ORR)
Time Frame: Assessed at baseline, after induction, and every 3 months during maintenance, up to approximately 24 months.
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ORR is defined as the proportion of patients achieving a confirmed Complete Response (CR) or Partial Response (PR) as assessed by the Independent Review Committee (IRC) according to RECIST v1.1. Patients must have measurable disease at baseline. |
Assessed at baseline, after induction, and every 3 months during maintenance, up to approximately 24 months.
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Safety and Tolerability
Time Frame: From enrollment until 90 days after the last dose of study treatment.
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Incidence, severity, and frequency of adverse events (AEs) and serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 6.0. |
From enrollment until 90 days after the last dose of study treatment.
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Collaborators and Investigators
Investigators
- Principal Investigator: Ningbo Liu, Doctor, Tianjin Medical University Cancer Institute and Hospital
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- E20261258
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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