Study of Carboplatin Plus Etoposide With or Without SHR-1316 in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Extensive-stage Small Cell Lung Cancer

Intervention / Treatment
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* Drug: SHR-1316
* Drug: Carboplatin
* Drug: Etoposide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria:• 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1316 + carboplatin + etoposide<br>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. | Drug: SHR-1316<br>* SHR-1316 intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6) and maintenance phase.<br>Drug: Carboplatin<br>* Carboplatin intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).<br>Drug: Etoposide<br>* Etoposide intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).<br>|
| Active Comparator: Placebo + carboplatin + etoposide<br>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. | Drug: Carboplatin<br>* Carboplatin intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).<br>Drug: Etoposide<br>* Etoposide intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).<br>Drug: Placebo<br>* Placebo intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6) and maintenance phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Overall Survival (OS) | Baseline until death from any cause | up to approximately 31 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Progression-Free Survival (PFS) as Assessed Using RECIST v1.1 |  | up to approximately 6 months | 
| Percentage of Participants With Objective Response (OR) as Assessed by the Investigator Using RECIST v1.1 | Baseline until partial response (PR) or complete response (CR), whichever occurs first | up to approximately 31 months | 
| Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 | First occurrence of PR or CR until PD or death, whichever occurs first | 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 |