A Single-Arm, Multicenter, Prospective Phase II Clinical Study of Iparomlimab and Tuvonralimab Injection Combined With Chemotherapy and Sequential Thoracic Radiotherapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 46
- 主要终点
- Progression-Free Survival
研究概览
简要总结
This study will evaluate the efficacy and safety of Iparomlimab and Tuvonralimab Injection in combination with Chemotherapy and Sequential Thoracic Radiotherapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer.
详细描述
This is a prospective, single-arm, multicenter clinical study assessing the efficacy and safety of Iparomlimab and Tuvonralimab Injection in combination with Chemotherapy and Sequential Thoracic Radiotherapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer. As well as, this study aimed to longitudinally monitor the dynamic changes of molecular residual disease in patients with extensive-stage small cell lung cancer to evaluate treatment efficacy and explore the potential application value of MRD as a biomarker for efficacy assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For voluntary signing of the informed consent form, participants aged 18 to 75 years (inclusive), regardless of gender, are eligible
- •Histologically or cytologically confirmed ES-SCLC (according to the Veterans Administration Lung Study Group [VALG] staging system)
- •Expected survival ≥ 3 months
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- •No prior systemic first-line therapy or immune checkpoint inhibitor treatment for ES-SCLC
- •Prior treatment with curative-intent surgery and adjuvant therapy (e.g., radiotherapy or chemotherapy), with a treatment-free interval of at least 6 months between the last dose of chemotherapy/radiotherapy/chemoradiotherapy and the diagnosis of ES-SCLC
- •According to RECIST v1.1 (Appendix 2), previously irradiated lesions can only be considered measurable if there is documented disease progression at that site after radiotherapy, and such lesions must not be the sole site of disease
- •Laboratory test results must meet the following criteria prior to enrollment: a) Hematology: No blood transfusion or hematopoietic growth factor administration within 14 days before enrollment; white blood cell count (WBC) ≥3.0×10^9/L; absolute neutrophil count (ANC) ≥1.5×10^9/L; platelets (PLT) ≥100×10^9/L; hemoglobin (HGB) ≥9.0 g/dL. b) Liver function: Non-liver metastasis subjects: Aspartate aminotransferase (AST) ≤2.5×ULN and alanine aminotransferase (ALT) ≤2.5×ULN. Liver metastasis subjects: ALT and AST ≤5×ULN; serum total bilirubin (TBIL) ≤1.5×ULN (except Gilbert syndrome, where TBIL ≤3.0 mg/dL). c) Renal function: Serum creatinine ≤1.5×ULN or calculated creatinine clearance (CrCl) ≥50 mL/min (using the Cockcroft-Gault formula in Appendix 3). d) Coagulation: International normalized ratio (INR) ≤1.5×ULN or activated partial thromboplastin time (APTT) ≤1.5×ULN (only for subjects not receiving anticoagulation therapy; subjects on stable-dose anticoagulants are eligible). e) Other tests confirming adequate cardiopulmonary function
- •Male patients with reproductive potential or female patients of childbearing potential must use effective contraception (e.g., oral contraceptives, intrauterine devices, or barrier methods combined with spermicides) during the study and continue for 6 months after treatment completion
- •For patients with HBV or HCV infection, the following criteria must be met: HBV-infected patients (HBsAg or HBV-DNA positive): Prior to the first treatment, HBV-infected patients must receive ≥3 days of guideline-recommended antiviral therapy with confirmed reduction in HBV-DNA levels upon retesting . Standard antiviral treatment must continue throughout the study period . HCV-infected subjects (HCVAb or HCV RNA positive): Must be in a stable condition as judged by the investigator. If already on antiviral therapy, treatment should be maintained during the study
- •Good compliance and cooperation with follow-up
排除标准
- •Patients with allergies or intolerance to the EP chemoradiotherapy regimen or any active/auxiliary components of the investigational drug
- •Active or untreated central nervous system (CNS) metastases identified by computed tomography (CT) or magnetic resonance imaging (MRI) during screening or prior radiographic assessments
- •Malignant effusions (pleural/ascites/pericardial) refractory to prior interventions (Defined as significant reaccumulation requiring repeat drainage or other interventions within 2 weeks, accompanied by symptomatic worsening)
- •Active autoimmune diseases , including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), antiphospholipid syndrome, granulomatosis with polyangiitis (Wegener's), Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis (MS)
- •Uncontrolled hypertension despite treatment with ≥1 antihypertensive agent(s) (Defined as systolic blood pressure (SBP) ≥160 mmHg or diastolic blood pressure (DBP) ≥100 mmHg, based on the average of ≥2 BP readings, despite ongoing antihypertensive therapy. Adjustment of treatment to improve these parameters is permitted.)
- •Moderate-to-severe pulmonary diseases that significantly impair lung function , including but not limited to interstitial lung disease (ILD), drug-induced pneumonitis, idiopathic pneumonia, or idiopathic pulmonary fibrosis (IPF)
- •Patients with active tuberculosis infection confirmed by medical history or CT examination, or those with a history of active tuberculosis infection within 1 year prior to enrollment
- •Severe infections within 4 weeks prior to initial treatment , including but not limited to hospitalization due to infectious complications, bacteremia, or severe pneumonia
- •Severe cardiovascular or cerebrovascular diseases within 3 months prior to initial treatment , including myocardial infarction, cerebrovascular accident, unstable arrhythmia, or unstable angina
- •History of allogeneic bone marrow transplantation or solid organ transplantation
- •Prior treatment with immune checkpoint inhibitors (ICIs) , including but not limited to anti-PD-1, anti-PD-L1, or anti-CTLA-4 agents
- •Use of systemic immunosuppressive therapy within 2 weeks prior to initial treatment , or anticipated need for systemic immunosuppressive therapy during the study treatment period
- •Participation in any other interventional clinical study or use of any other investigational product within 4 weeks prior to signing the informed consent form
- •History of abdominal or tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within 1 month prior to initial treatment
- •Major vascular disease occurring within 3 months prior to initial treatment (e.g., aortic aneurysm requiring surgical repair)
- •Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study
- •Positive for human immunodeficiency virus (HIV) antibody
- •History of schizophrenia or psychotropic drug abuse
- •Other factors considered by the investigator to make the subject unsuitable for participation in the study
研究组 & 干预措施
Iparomlimab and Tuvonralimab Injection Combined with EP and Sequential Thoracic Radiotherapy
Subjects first underwent induction therapy, receiving 4 to 6 cycles of Iparomlimab and Tuvonralimab Injection combined with etoposide and cisplatin. Upon completion of treatment, imaging evaluation was performed. Subjects who achieved a response of CR, PR, or SD with good local control proceeded to receive sequential thoracic radiotherapy (TRT), followed by maintenance therapy with Iparomlimab and Tuvonralimab Injection as a single agent.
干预措施: Iparomlimab and Tuvonralimab Injection (Drug)
Iparomlimab and Tuvonralimab Injection Combined with EP and Sequential Thoracic Radiotherapy
Subjects first underwent induction therapy, receiving 4 to 6 cycles of Iparomlimab and Tuvonralimab Injection combined with etoposide and cisplatin. Upon completion of treatment, imaging evaluation was performed. Subjects who achieved a response of CR, PR, or SD with good local control proceeded to receive sequential thoracic radiotherapy (TRT), followed by maintenance therapy with Iparomlimab and Tuvonralimab Injection as a single agent.
干预措施: Etoposide (Drug)
Iparomlimab and Tuvonralimab Injection Combined with EP and Sequential Thoracic Radiotherapy
Subjects first underwent induction therapy, receiving 4 to 6 cycles of Iparomlimab and Tuvonralimab Injection combined with etoposide and cisplatin. Upon completion of treatment, imaging evaluation was performed. Subjects who achieved a response of CR, PR, or SD with good local control proceeded to receive sequential thoracic radiotherapy (TRT), followed by maintenance therapy with Iparomlimab and Tuvonralimab Injection as a single agent.
干预措施: Cisplatin (Drug)
Iparomlimab and Tuvonralimab Injection Combined with EP and Sequential Thoracic Radiotherapy
Subjects first underwent induction therapy, receiving 4 to 6 cycles of Iparomlimab and Tuvonralimab Injection combined with etoposide and cisplatin. Upon completion of treatment, imaging evaluation was performed. Subjects who achieved a response of CR, PR, or SD with good local control proceeded to receive sequential thoracic radiotherapy (TRT), followed by maintenance therapy with Iparomlimab and Tuvonralimab Injection as a single agent.
干预措施: Targeted Radiation Therapy (Radiation)
结局指标
主要结局
Progression-Free Survival
时间窗: 1 year
PFS was defined as the time from the first administration of the study drug to the first occurrence of objective tumor progression or death from any cause, whichever occurred first.
次要结局
- Disease Control Rate(1 year)
- Duration of Response(1 year)
- Thoracic Local Control Rate(1 year)
- Overall Survival(1 year)
- Objective Response Rate(1 year)