Effectiveness Study of Nivolumab Compared to Chemotherapy in Patients With Relapsed Small-cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to compare the overall survival of nivolumab versus chemotherapy in subjects with relapsed SCLC.

Official Title
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An Open-label, Randomized, Phase 3 Study of Nivolumab or Chemotherapy in Subjects With Relapsed Small-cell Lung Cancer After Platinum-based First Line Chemotherapy (CheckMate 331: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 331)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Topotecan
* Drug: Amrubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed small cell lung cancer (SCLC) Subjects with either limited or extensive disease stage at the initial diagnosis Must have recurrence or progression after platinum-based first-line chemotherapy or chemoradiation therapy for the treatment of limited or extensive disease stage SCLC Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria: Untreated or symptomatic central nervous system (CNS) metastases Prior therapy with anti-PD-1, anti-PDL1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody Inadequate hematologic or hepatic function

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A Nivolumab<br>Nivolumab intravenous infusion as specified | Drug: Nivolumab<br> <br> |
| Active Comparator: Arm B Chemotherapy Topotecan<br>Topotecan as specified | Drug: Topotecan<br> <br> |
| Active Comparator: Arm B Chemotherapy Amrubicin<br>Amrubicin intravenous infusion as specified (upon investigator's choice, where locally approved for 2nd line SCLC treatment) | Drug: Amrubicin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | The time from randomization to the date of death, data was based on Kaplan-Meier Estimates. A participant who has not died will be censored at last known date alive. | OS was followed continuously while participants were on the study drug and every 3 months, minimum follow up for overall survival was 15.8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time from randomization to the date of the first documented tumor progression based on investigator assessment (per RECIST 1.1), or death due to any cause. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored on the date they were randomized. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to initiation of the subsequent anti-cancer therapy. Progressive disease (PD)= At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must demonstrate an absolute increase of at least 5 mm. | From randomization to the date of first documented tumor progression, or death due to any cause. Tumor response assessed every 6 weeks from first dose until week 30, and every 12 weeks (Up to approximately 80 months) | 
| Objective Response Rate (ORR) | ORR is defined as the percentage of randomized participants whose best overall response (BOR) from baseline is either a complete response (CR) or partial response (PR) based on investigator assessment per RECIST 1.1 criteria. For participants without documented progression or subsequent anti-cancer therapy, all available response designations will contribute to the BOR determination. For participants who continue nivolumab beyond progression, the BOR should be determined based on tumor assessments before initial RECIST 1.1 defined progression. CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD)= At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must demonstrate an absolute increase of at least 5 mm. | From randomization to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (Up to approximately 80 months) |