Exploration of Treatment Strategies After Concurrent Chemoradiotherapy for LS-SCLC Guided by MRD

Official title

Exploration of Treatment Strategies After Concurrent Chemoradiotherapy for Limited-stage Small Cell Lung Cancer (LS-SCLC) Guided by Molecular Residual Disease (MRD)

Overview

This study plans to enroll limited-stage small cell lung cancer (LS-SCLC) patients who have achieved disease control after concurrent chemoradiotherapy (cCRT). Tissue samples collected at initial diagnosis and serial peripheral blood samples obtained at multiple post-cCRT timepoints will be analyzed using targeted next-generation sequencing to investigate the correlation between molecular residual disease (MRD) status and tumor recurrence/metastasis. For patients with MRD-positive results, a therapeutic strategy combining immunotherapy with anti-angiogenic agents will be implemented with the aim of improving clinical outcomes.

Interventions

• Drug Adebrelimab Injection
  Patients with MRD Positive will receive adebrelimab (1200 mg, D1, Q3W) , followed by ctDNA monitoring every 2 months (Year 1) and every 3 months (Year 2).The above treatment regimen will be maintained until disease progression, intolerable toxicity, completion of two years of treatment, subject-initiated withdrawal, or investigator-determined discontinuation.
• Drug Apatinib Mesylate Tablets
  Apatinib Mesylate Tablets (250 mg, QD) , followed by ctDNA monitoring every 2 months (Year 1) and every 3 months (Year 2).The above treatment regimen will be maintained until disease progression, intolerable toxicity, completion of two years of treatment, subject-initiated withdrawal, or investigator-determined discontinuation.

Primary outcome measures

• Negative conversion rate of MRD [Time frame: MRD is assessed at 60-day intervals during the first year and 90-day intervals during the second year, until disease progression, study discontinuation for any reason, or completion of 2 years of follow-up, whichever occurs first.]

Secondary outcome measures (4)

• PFS [Time frame: Imaging assessments are performed every 3 months. After each assessment, treatment response is evaluated by senior experts according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The maximum follow-up duration is 2 years.]
• OS [Time frame: Imaging assessments are performed every 3 months. After each assessment, treatment response is evaluated by senior experts according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The maximum follow-up duration is 2 years.]
• Time to conversion to MRD negativity [Time frame: MRD is assessed at 60-day intervals during the first year and 90-day intervals during the second year, until disease progression, study discontinuation for any reason, or completion of 2 years of follow-up, whichever occurs first.]
• Duration of negative conversion after medication in MRD-positive patients [Time frame: MRD is assessed at 60-day intervals during the first year and 90-day intervals during the second year, until disease progression, study discontinuation for any reason, or completion of 2 years of follow-up, whichever occurs first.]

Eligibility criteria

Inclusion criteria

• Signed informed consent; age >18 and <80 years;
• Histologically or cytologically confirmed limited-stage small cell lung cancer (LS-SCLC);
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1;
• Patients who have achieved disease stabilization after concurrent or sequential chemoradiotherapy;
• Patients who had not received previous immune checkpoint inhibitor treatment;
• Patients with MRD-positive status following concurrent chemoradiotherapy;
• Willingness to provide clinical-pathological data, imaging studies, and other required materials for research purposes; compliance with follow-up procedures, including blood sample collection at predefined efficacy evaluation timepoints; and agreement to use the collected data for subsequent research analyses.

Exclusion criteria

• Have other malignant tumors;
• Autoimmune disorders that are not amenable to PD-L1 inhibitor therapy;
• Prior exposure to other anti-angiogenic small molecule TKIs such as erlotinib or anti-angiogenic monoclonal antibodies such as bevacizumab (except locally infused bevacizumab); or participation in a clinical trial of another antineoplastic agent within 4 weeks prior to the first dose of ; or prior treatment with a paclitaxel;
• Uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg despite optimal pharmacologic therapy);
• Class II or greater myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc intervals ≥450 ms in men and ≥470 ms in women). According to NYHA criteria, grade III-IV cardiac insufficiency, or cardiac color ultrasound suggests that the left ventricular ejection fraction (LVEF) is <50% have had a myocardial infarction within 6 months prior to enrollment, New York Heart Association class II or higher heart failure, uncontrolled angina pectoris, uncontrolled severe ventricular arrhythmia, clinically significant pericardial disease, or ECG suggestive of acute ischemia or active conduction system abnormalities; (6) uncontrolled angina pectoris, uncontrolled severe ventricular arrhythmias, clinically significant pericardial disease, or ECG suggestive of acute ischemia or active conduction system abnormalities.
• Uncontrolled co-morbidities including, but not limited to, poorly controlled diabetes mellitus, diabetic peripheral lesions , persistent infections, or psychiatric or social conditions that may interfere with the subject's ability to comply;
• Abnormal coagulation (INR > 1.5 or Prothrombin Time (PT) > ULN + 4 seconds or APTT > 1.5 ULN), hemorrhagic symptoms, or on thrombolytic or anticoagulant therapy;
• Known hereditary or acquired bleeding and thrombotic disorders such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.;
• Significant coughing up of fresh blood or hemoptysis of one-half teaspoon (2.5 ml) per day or more within 2 months prior to entry into the study ;
• Failure to receive specified treatment or change in treatment regimen prior to disease progression;
• Unable to cooperate with the study in accordance with the established clinical follow-up period;
• Unable to accept or provide the specified means of efficacy assessment such as imaging.
• Pregnant or lactating women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University Cancer Hospital & Institute — Beijing

Identifiers

NCT: NCT07357532 · 2025YJZ103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗