An Investigational Immuno-therapy Study of Nivolumab, or Nivolumab in Combination With Ipilimumab, or Placebo in Patients With Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) After Completion of Platinum-based Chemotherapy

Study Overview
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Brief Summary
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In this study, all patients must have already completed first-line chemotherapy to treat extensive-stage disease small cell lung cancer. The purpose of this study is to show that nivolumab, or nivolumab plus ipilimumab followed by nivolumab by itself, will prolong overall survival when administered as consolidation treatment in patients that are stable or responding after chemotherapy. Patients receiving treatment will be compared with patients taking placebo.

Official Title
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A Randomized, Multicenter, Double-Blind, Phase 3 Study of Nivolumab, Nivolumab in Combination With Ipilimumab, or Placebo as Maintenance Therapy in Subjects With Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) After Completion of Platinum-based First Line Chemotherapy (CheckMate 451: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 451)

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: Nivolumab
* Biological: Ipilimumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with histologically or cytologically confirmed extensive stage disease SCLC Ongoing response of stable disease or better following 4 cycles of platinum-based first line chemotherapy Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: Subjects with symptomatic Central Nervous System (CNS) metastases Subjects receiving consolidative chest radiation Subjects with active, known, or suspected autoimmune disease are excluded All side effects attributed to prior anti-cancer therapy must have resolved to Grade 1 or baseline Other protocol-defined inclusion/exclusion criteria apply

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab monotherapy<br>Nivolumab intravenous fusion | Biological: Nivolumab<br> <br> * Other names: Opdivo;|
| Experimental: Nivolumab and ipilimumab combination therapy<br>Nivolumab and ipilimumab intravenous fusion | Biological: Nivolumab<br> <br> * Other names: Opdivo;Biological: Ipilimumab<br> <br> * Other names: Yervoy;|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) of Nivolumab + Ipilimumab Versus Placebo In The Global Population | OS was defined as the time from randomization to the date of death. A participant who had not died was censored at last known alive date. OS was followed up during the blinded study drug treatment and every 3 months via in-person or phone contact after participant discontinued the blinded study drug | From randomization to 400 deaths across the two treatment groups (Nivo+Ipi vs Placebo) (up to approximately 37 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) of Nivolumab Versus Placebo | Overall Survival (OS) comparing nivolumab monotherapy versus placebo. OS was defined as the time from randomization to the date of death. A participant who had not died was censored at last known alive date. OS was followed up during the blinded study drug treatment and every 3 months via in-person or phone contact after participant discontinued the blinded study drug. | From randomization to the date of death or last known alive date (up to approximately 73 months) | 
| Overall Survival (OS) of Nivolumab + Ipilimumab Versus Nivolumab | Overall Survival (OS) comparing Nivolumab + Ipilimumab Versus Nivolumab. OS was defined as the time from randomization to the date of death. A participant who had not died was censored at last known alive date. OS was followed up during the blinded study drug treatment and every 3 months via in-person or phone contact after participant discontinued the blinded study drug. | From randomization to the date of death or last known alive date (up to approximately 73 months) | 
| Progression Free Survival (PFS) Per BICR | PFS was defined as the time between the date of randomization and the first date of documented progression as determined by Blind Independent Central Review (BICR) or death due to any cause, whichever occurred first. Participants who died with no reported progression were considered to have progressed on the date of death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment on or prior to initiation of the subsequent anti-cancer therapy. Participants who did not have any on study tumor assessments and did not die (or died after initiation of the subsequent anti- cancer therapy) were censored on their date of randomization. Participants who started any subsequent anti- cancer therapy without a prior reported Progressive Disease (PD) per BICR were censored at the last evaluable tumor assessment on or prior to initiation of the subsequent anti-cancer therapy. | From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 73 months) | 
| Overall Survival (OS) in Tumor Mutational Burden (TMB) High and Low Subgroups by TMB Cutoff In The Global Population | Tumor mutational burden (TMB) is measured using FoundationOne CDxTM (F1CDx) assay, a comprehensive genomic profile (CGP) assay based on baseline tumor tissue. TMB is defined as the number of somatic, coding, base substitution, and indel mutations per megabase of genome examined. OS in TMB by the following cutoff points: ≥10 mutations/mb, < 10 mutations/mb, ≥13 mutations/mb, <13 mutations/mb | From randomization to the date of death or last known alive date (up to approximately 73 months) | 
| Progression Free Survival (PFS) Per BICR in Tumor Mutational Burden (TMB) High and Low Subgroups by TMB Cutoff In The Global Population | Tumor mutational burden (TMB) is measured using FoundationOne CDxTM (F1CDx) assay, a comprehensive genomic profile (CGP) assay based on baseline tumor tissue. TMB is defined as the number of somatic, coding, base substitution, and indel mutations per megabase of genome examined. PFS in TMB by the following cutoff points: ≥10 mutations/mb, < 10 mutations/mb, ≥13 mutations/mb, <13 mutations/mb. | From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 73 months) |