Randomized, Double-blinded, Placebo Controlled, Multicenter, Phase III Study of Carboplatin Plus Etoposide With or Without SHR-1316 in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)
试验速览
- 阶段
- 3 期
- 入组人数
- 462
- 试验地点
- 2
- 主要终点
- Duration of Overall Survival (OS)
研究概览
简要总结
This randomized, double-blinded, placebo-controlled phase III, multicenter study is designed to evaluate the safety and efficacy of SHR-1316 in combination with carboplatin plus (+) etoposide compared with treatment with placebo + carboplatin + etoposide in chemotherapy-naive participants with ES-SCLC.
详细描述
Participants will be randomized in a 1:1 ratio to receive either SHR-1316 + carboplatin + etoposide or placebo + carboplatin + etoposide for 4-6 cycles in the induction phase followed by maintenance with SHR-1316 or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD or or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Age >= 18 years and <= 75 years
- •Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system)
- •Eastern Cooperative Oncology Group performance status of 0 or 1
- •No prior systemic treatment or immune checkpoint inhibitor treatment for ES-SCLC
- •At least 6 months treatment-free period since last chemo/radiotherapy with curative intent for limited-stage SCLC
- •Measurable disease, as defined by RECIST v1.1
- •Adequate hematologic and end organ function
- •Patients must submit a pre-treatment tumor tissue sample during the study.
- •Signed inform consent form
排除标准
- •Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation
- •Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ≥ 1 week prior to randomization
- •Leptomeningeal disease
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Uncontrolled or symptomatic hypercalcemia
- •Malignancies other than SCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
- •History of autoimmune disease, including but not limited to myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease
- •Prior treatment with immune checkpoint blockade therapies
- •Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first administration of study treatment. Inhaled or topical steroids, and adrenal replacement steroid are permitted in the absence of active autoimmune disease.
- •Significant cardiovascular disease
- •Prior allogeneic bone marrow transplantation or solid organ transplant
- •Treatment with systemic immunosuppressive medications within 2 weeks prior to randomization
- •History of hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, carboplatin or etoposide
- •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
研究组 & 干预措施
SHR-1316 + carboplatin + etoposide
Participants will receive SHR-1316 intravenously in combination with carboplatin and etoposide during the induction phase (Cycles 1-4 or 6). Thereafter, participants will receive maintenance (after induction phase) SHR-1316 until persistent radiographic PD, intolerable toxicity or withdrawal of consent.
干预措施: SHR-1316 (Drug)
SHR-1316 + carboplatin + etoposide
Participants will receive SHR-1316 intravenously in combination with carboplatin and etoposide during the induction phase (Cycles 1-4 or 6). Thereafter, participants will receive maintenance (after induction phase) SHR-1316 until persistent radiographic PD, intolerable toxicity or withdrawal of consent.
干预措施: Carboplatin (Drug)
SHR-1316 + carboplatin + etoposide
Participants will receive SHR-1316 intravenously in combination with carboplatin and etoposide during the induction phase (Cycles 1-4 or 6). Thereafter, participants will receive maintenance (after induction phase) SHR-1316 until persistent radiographic PD, intolerable toxicity or withdrawal of consent.
干预措施: Etoposide (Drug)
Placebo + carboplatin + etoposide
Participants will receive placebo intravenously in combination with carboplatin and etoposide during the induction phase (Cycles 1-4 or 6). Thereafter, participants will receive maintenance (after induction phase) placebo until persistent radiographic PD, intolerable toxicity or withdrawal of consent.
干预措施: Carboplatin (Drug)
Placebo + carboplatin + etoposide
Participants will receive placebo intravenously in combination with carboplatin and etoposide during the induction phase (Cycles 1-4 or 6). Thereafter, participants will receive maintenance (after induction phase) placebo until persistent radiographic PD, intolerable toxicity or withdrawal of consent.
干预措施: Etoposide (Drug)
Placebo + carboplatin + etoposide
Participants will receive placebo intravenously in combination with carboplatin and etoposide during the induction phase (Cycles 1-4 or 6). Thereafter, participants will receive maintenance (after induction phase) placebo until persistent radiographic PD, intolerable toxicity or withdrawal of consent.
干预措施: Placebo (Drug)
结局指标
主要结局
Duration of Overall Survival (OS)
时间窗: up to approximately 31 months
Baseline until death from any cause
次要结局
- Duration of Progression-Free Survival (PFS) as Assessed Using RECIST v1.1(up to approximately 6 months)
- Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1(up to approximately 31 months)
- Percentage of Participants With Objective Response (OR) as Assessed by the Investigator Using RECIST v1.1(up to approximately 31 months)
- Percentage of Participants Alive and Without PD, as Assessed by the Investigator Using RECIST v1.1, at 6 Months and 1 Year(6 months, 1 year)
- Percentage of Participants Alive at 1 Year and 2 Years(1 year, 2 years)
- Percentage of Participants with Adverse Events Or Serious Adverse Events.(up to approximately 31 months)