A Study of Nivolumab and Ipilimumab in Untreated Participants With Stage 3 Non-small Cell Lung Cancer (NSCLC) That is Unable or Not Planned to be Removed by Surgery

Study Overview
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Brief Summary
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The primary purpose of the study is to compare the effectiveness of nivolumab plus concurrent chemoradiotherapy (CCRT) followed by nivolumab plus ipilimumab vs CCRT followed by durvalumab in participants with untreated Locally Advanced Non-small Cell Lung Cancer (LA NSCLC).

Official Title
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A Phase 3, Randomized, Open Label Study to Compare Nivolumab Plus Concurrent Chemoradiotherapy (CCRT) Followed by Nivolumab Plus Ipilimumab or Nivolumab Plus CCRT Followed by Nivolumab vs CCRT Followed by Durvalumab in Previously Untreated, Locally Advanced Non-small Cell Lung Cancer (LA NSCLC)

Conditions
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Non-Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Biological: nivolumab
* Biological: ipilimumab
* Biological: durvalumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Locally advanced stage IIIA, IIIB, or IIIC (T1-2 N2-3 M0, T3 N1-3 M0, or T4 N0-3 M0) pathologically-confirmed NSCLC, according to 8th TNM classification. Participants who are not planned for potential curative surgical resection are eligible. Newly diagnosed and treatment-naïve, with no prior local or systemic anticancer therapy given as primary therapy for locally advanced disease Exclusion Criteria: Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator would preclude the participant from adhering to the protocol or would increase the risk associated with study participation Active infection requiring systemic therapy within 14 days prior to randomization History of organ or tissue transplant that requires systemic use of immune suppressive agents Prior thoracic radiotherapy 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: nivolumab + CCRT + ipilimumab<br>Concurrent chemoradiotherapy (CCRT) | Biological: nivolumab<br>* Specified dose on specified days<br>Biological: ipilimumab<br>* Specified dose on specified days<br>|
| Experimental: Arm B: nivolumab + CCRT<br>Concurrent chemoradiotherapy (CCRT) | Biological: nivolumab<br>* Specified dose on specified days<br>|
| Experimental: Arm C: CCRT + durvalumab<br>Concurrent chemoradiotherapy (CCRT) | Biological: durvalumab<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) by RECIST 1.1 per Blinded Independent Central Review (BICR) for Arm A vs Arm C |  | Up to 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) for Arm A vs Arm C |  | Up to 7 years | 
| PFS by RECIST 1.1 per BICR for Arm B vs Arm C |  | Up to 7 years | 
| OS for Arm B vs Arm C |  | Up to 7 years | 
| PFS by RECIST 1.1 per BICR for Arm A vs Arm B |  | Up to 7 years | 
| OS for Arm A vs Arm B |  | Up to 7 years | 
| Objective Response Rate (ORR) by RECIST 1.1 per BICR |  | Up to 7 years | 
| Duration of Response (DoR) by RECIST 1.1 per BICR |  | Up to 7 years | 
| Time to Response (TTR) by RECIST 1.1 per BICR |  | Up to 7 years | 
| PFS by RECIST 1.1 per Investigator assessment |  | Up to 7 years | 
| ORR by RECIST 1.1 per Investigator assessment |  | Up to 7 years | 
| DoR by RECIST 1.1 per Investigator assessment |  | Up to 7 years | 
| TTR by RECIST 1.1 per Investigator assessment |  | Up to 7 years | 
| Time to Death or Distant Metastases (TTDM) by RECIST 1.1 per Investigator assessment |  | Up to 7 years | 
| Incidence of Adverse Events (AEs) |  | Up to 7 years | 
| Incidence of Serious Adverse Events (SAEs) |  | Up to 7 years | 
| Incidence of select AEs |  | Up to 7 years | 
| Proportion of participants without symptom deterioration based on NSCLC-SAQ | Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ) | Up to 7 years |