Study of Low-Dose Radiotherapy Concurrent Cisplatin/Carboplatin Plus Etoposide With Serplulimab for Patients With ES-SCLC

Study Overview
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Brief Summary
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This is a Phase II, single arm, multicenter study designed to evaluate the safety and efficacy of low-dose radiotherapy (LDRT) concurrent cisplatin/carboplatin plus etoposide with serplulimab in participants who have extensive-stage small cell lung cancer (ES-SCLC) and are chemotherapy-navïe for their extensive-stage disease.

Official Title
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Phase II, Single-Arm Study of Low-Dose Radiotherapy (LDRT) Concurrent Cisplatin/Carboplatin Plus Etoposide With Serplulimab for Patients With Extensive-Stage Small Cell Lung Cancer

Conditions
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Extensive-stage Small-cell Lung Cancer

Intervention / Treatment
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* Drug: serplulimab
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: Etoposide
* Radiation: Thoracic radiation therapy (TRT)


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Histologically or cytologically confirmed ES-SCLC No prior treatment for ES-SCLC Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation. ECOG performance status of 0 or 1 Life expectancy >= 3 months Adequate hematologic and end-organ function For participants receiving therapeutic anticoagulation: stable anticoagulant regimen Negative human immunodeficiency virus (HIV) test at screening Negative hepatitis B surface antigen (HBsAg) test at screening Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: Negative total hepatitis B core antibody (HBcAb), or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test. The HBV DNA test will be performed only for participants who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for participants who have a positive HCV antibody test. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm Main Exclusion Criteria: Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases Participants with pulmonary artery invasion History of leptomeningeal disease Uncontrolled tumor-related pain Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Uncontrolled or symptomatic hypercalcemia Active or history of autoimmune disease or immune deficiency History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan Active tuberculosis Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina History of malignancy other than small cell lung cancer (SCLC) within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab<br>Participants will receive the following treatment regimens: LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab. Induction treatment will be administered on a 21-day cycle for four cycles. Concurrent radiation therapy will be conducted from Day 1 - Day 5 in the first cycle. Following the induction phase, participants will continue maintenance therapy with serplulimab and thoracic radiation therapy (30Gay/10f）. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first). | Drug: serplulimab<br>* Serplulimab will be administered by intravenous infusion at a dose of 4.5mg/kg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status.<br>Drug: Cisplatin<br>* Cisplatin will be administered as intravenous infusion at a dose of 75 mg per meter squared (75 mg/m^2) after completion of serplulimab on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).<br>Drug: Carboplatin<br>* Carboplatin will be administered as intravenous infusion at a dose of area under the concentration-time curve (AUC) of 5 mg/mL/min on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).<br>Drug: Etoposide<br>* Etoposide will be administered intravenously at a dose of 100 mg/m^2 on Days 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4).<br>Radiation: Thoracic radiation therapy (TRT)<br>* Participants will receive concurrent thoracic radiation therapy (TRT) treatment, in once daily fractions, 3 Gy per fraction, to a target dose of 15 Gy in 5 fractions from Day 1-Day 5 in the first cycle.Following the induction phase, participants will continue maintenance therapy with serplulimab thoracic radiation therapy (TRT) treatment, in once daily fractions, 3 Gy per fraction, to a target dose of 30 Gy in 10 fractions in the fifth and sixth cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | The time from the date of first dosing of durvalumab to the first appearance of objective disease progression (according to RECIST1.1) or death from any cause (if it occurs before disease progression). | Baseline up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS Rate at 6 Months and 1 Year | PFS rate at 6 months and 1 year, defined as the proportion of patients who have not experienced disease progression or death from any cause at 6 months and 1 year separately, as determined by the investigator according to RECIST v1.1. | Baseline up to 1 year | 
| Overall Survival (OS) | OS, defined as the time from initiation of study treatment to death from any cause. | Baseline up to approximately 24 months | 
| OS Rate at 1 Year and 2 Years | OS rate at 1 year and 2 years, defined as the proportion of patients who have not experienced death from any cause at 1 year and 2 years. | Baseline to 2 years or death, whichever occurs first. | 
| Duration of response (DOR) | defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. | Baseline to disease progression or death from any cause (whichever occurs first)(up to approximately 24 months) | 
| Disease control rate (DCR) | defined as the proportion of participants who have a best overall response of CR or PR or stable disease (SD), as determined by the investigator according to RECIST v1.1. | Baseline up to approximately 24 months | 
| Percentage of Participants With Adverse Event |  | Baseline up to approximately 36 months |