Clinical trial NCT06869239: Prediction of Response to PD-L1 Inhibitor After Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer Using Multi-omics-based Liquid Biopsy
Official title: Prediction of Response to PD-L1 Inhibitor After Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer Using Multi-omics-based Liquid Biopsy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Limited-stage Small Cell Lung Cancer (LS-SCLC)
Keywords: LS-SCLC
immunotherapy
liquid biopsy
high-dose radiotherapy
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2025-03-11
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: LS-SCLC with PD-L1 inhibitor after Chemoradiotherapy

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.


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.

Primary outcomes:
measure: Progression-free survival
timeFrame: From enrollment to disease progression or death due to any cause, whichever occurs first, assessed up to 3 years.
Secondary outcomes:
measure: Overall survival
timeFrame: The time from enrollment to death due to any cause, assessed up to 3 years.
measure: Objective response rate
timeFrame: Up to 3 years
measure: Disease control rate
timeFrame: Up to 3 years
measure: Incidence and severity of adverse events
timeFrame: From enrollment to 30 days after the end of study treatment.
Other outcomes:
measure: Blood biomarker analysis
timeFrame: Up to 3 years
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital & Institute
state: Beijing
Study officials:
References: