Prediction of Response to PD-L1 Inhibitor After Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer Using Multi-omics-based Liquid Biopsy

NCT ID: NCT06869239

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 65 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-02-25
• Study Completion Date: 2028-01-03

Brief Summary

This study aims to explore the efficacy and safety of immunotherapy (PD-L1 inhibitor) maintenance following high-dose hyperfractionated simultaneous integrated boost radiotherapy concurrent chemotherapy in patients with limited-stage small cell lung cancer (LS-SCLC). This study is a prospective observational study. Additionally, liquid biopsy technology will be employed to identify biomarkers that can predict the efficacy of PD-L1 inhibitor after chemoradiotherapy in LS-SCLC.

Conditions

Limited-stage Small Cell Lung Cancer (LS-SCLC)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

PD-L1 inhibitor after chemoradiotherapy

PD-L1 inhibitor maintenance following high-dose hyperfractionated simultaneous integrated boost radiotherapy concurrent chemotherapy in patients with limited-stage small cell lung cancer

Etoposide + cisplatin/carboplatin

Intervention Type: DRUG

Four courses of intravenous cisplatin (75 mg/m² of body surface area on day 1 or divided into 3 days of each cycle) or carboplatin (area under the curve of 5 mg/mL per min on day 1 of each cycle) and intravenous etoposide (100 mg/m² of body surface area on days 1-3) every 3 weeks

Thoracic radiotherapy

Intervention Type: RADIATION

High-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) concurrent with chemotherapy initiated at the beginning of cycles 1-3

Prophylactic cranial irradiation (PCI)

Intervention Type: RADIATION

PCI (25Gy in 10 fractions, once daily over two weeks) 3-4 weeks post-chemoradiotherapy for patients achieving PR or CR

PD-L1 inhibitor

Intervention Type: DRUG

Maintenance therapy with PD-L1 inhibitors (Durvalumab 1500 mg Q4W or Atezolizumab 1200 mg Q3W or Sugemalimab 1200 mg Q3W or Adebrelimab 1200 mg Q3W) post-PCI until disease progression, death, or intolerable toxicity, up to 2 years

Interventions

Etoposide + cisplatin/carboplatin

Four courses of intravenous cisplatin (75 mg/m² of body surface area on day 1 or divided into 3 days of each cycle) or carboplatin (area under the curve of 5 mg/mL per min on day 1 of each cycle) and intravenous etoposide (100 mg/m² of body surface area on days 1-3) every 3 weeks

Intervention Type: DRUG

Thoracic radiotherapy

High-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) concurrent with chemotherapy initiated at the beginning of cycles 1-3

Intervention Type: RADIATION

Prophylactic cranial irradiation (PCI)

PCI (25Gy in 10 fractions, once daily over two weeks) 3-4 weeks post-chemoradiotherapy for patients achieving PR or CR

Intervention Type: RADIATION

PD-L1 inhibitor

Maintenance therapy with PD-L1 inhibitors (Durvalumab 1500 mg Q4W or Atezolizumab 1200 mg Q3W or Sugemalimab 1200 mg Q3W or Adebrelimab 1200 mg Q3W) post-PCI until disease progression, death, or intolerable toxicity, up to 2 years

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Age 18-75 years, male or female;
• 2. Histologically or cytologically confirmed limited-stage small cell lung cancer (LS-SCLC) (AJCC, 8th edition);
• 3. No more than 2 cycles of chemotherapy or no previous systemic therapy;
• 4. ECOG PS 0-1;
• 5. Measurable disease, as defined by RECIST v1.1 (tumor lesions long axis≥10mm, lymph nodes short axis ≥15mm);
• 6. Life expectancy ≥3 months;
• 7. Adequate pulmonary function;
• 8. Adequate hematologic and end-organ function, defined by the following criteria:

1. Hematology

• Hemoglobin (HGB) ≥90 g/L;
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L;
• Platelet count (PLT) ≥ 100 x 10^9/L;
• White blood cell count (WBC) ≥ 3.0 x 10^9/L;

2. Serum chemistry

• Serum albumin (ALB) ≥ 30 g/L;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x ULN;
• Total bilirubin (TBIL) ≤1.5 ULN; Note: Patients diagnosed with Gilbert's syndrome (persistent or recurrent hyperbilirubinemia [mainly unconjugated bilirubin] without evidence of hemolysis or liver pathology) after consultation with their physician can be allowed;
• Creatinine ≤ 1.5 ULN;
• 9. Women of childbearing age must have taken reliable contraceptive measures or undergone a negative pregnancy test (serum or urine) within 7 days prior to enrollment. Both men and women of childbearing age must agree to maintain adequate contraceptive measures throughout the study and for 6 months following the completion of treatment;
• 10. Patients must voluntarily participate in this study, sign the informed consent form, demonstrate good compliance, and actively cooperate with follow-up procedures.

Exclusion Criteria

• 1. Histological mixture of SCLC and NSCLC components;
• 2. Extensive-stage SCLC;
• 3. Patients with a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, or those planned for transplantation;
• 4. Treatment with immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 14 days prior to the first dose of PD-L1 inhibitor, except for intranasal and inhaled corticosteroids or low-dose systemic steroids (i.e., ≤10 mg/day prednisolone or equivalent);
• 5. History of hypersensitivity to etoposide, cisplatin, PD-L1 antibody, or excipients in the formulation; or history of severe allergic reactions to other monoclonal antibodies;
• 6. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment;
• 7. Active or history of autoimmune disease or immune deficiency (including but not limited to autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism);

Note:

• Patients with vitiligo or alopecia are eligible for this study;
• Patients with stable hypothyroidism undergoing hormone replacement therapy (e.g., Hashimoto's syndrome) are eligible for this study;

• 8. Poorly controlled asthma despite systemic treatment, such as bronchodilators; Note: Patients with complete remission of asthma during childhood and no need for any intervention in adulthood can be allowed;
• 9. Urinalysis shows proteinuria ≥ ++ or confirmed 24-hour urine protein ≥ 1.0g;
• 10. Malignancies other than LS-SCLC, with the following exceptions:
• Adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix;
• Malignancy that has been treated with curative intent, with no known active disease for ≥5 years prior to the first dose of the study treatment, and with a low potential risk of recurrence;

• 11. Human immunodeficiency virus (HIV) infection or known to have acquired immunodeficiency syndrome (AIDS);
• 12. Significant cardiovascular disease within 6 months prior to enrollment, such as myocardial infarction, severe/unstable angina, New York Heart Association cardiac disease (class II or greater), poorly controlled arrhythmias (including QTcF interval >450 ms for males and >470 ms for females, with QTcF interval calculated using the Fridericia formula), and symptomatic congestive heart failure;
• 13. Severe infections within 4 weeks prior to first dose of study treatment, including but not limited to infections requiring intravenous antibiotics, antifungal, or antiviral agents , or unexplained fever ≥38.5°C occurring during the screening period or before the first dose of the study treatment;
• 14. Active tuberculosis, hepatitis B (HBV-DNA ≥ 500 IU/ml), hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the assay), or co-infection with both hepatitis B and C;
• 15. Treatment with any other investigational agent with therapeutic intent within 4 weeks prior to the first dose of the study treatment;
• 16. History of abuse of psychotropic drugs or drug addiction;
• 17. Patients with other severe physical or mental illnesses or abnormal laboratory test results that may increase the risk of participating in the study, or interfere with the study results, as well as those whom the investigator deems unsuitable for participation in the study for other reasons.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Peking University Cancer Hospital & Institute

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Anhui Shi

Role: CONTACT

anhuidoctor@163.com

8601088196087

Jiayi Yu

Role: CONTACT

8601088196087

Facility Contacts

Anhui Shi

Role: primary

anhuidoctor@163.com

8601088196087

Jiayi Yu

Role: backup

8601088196087

Other Identifiers

BRWEP2024W032150110

Identifier Type: -

Identifier Source: org_study_id