REGN2810 (Anti-PD-1 Antibody), Platinum-based Doublet Chemotherapy, and Ipilimumab (Anti-CTLA-4 Antibody) Versus Pembrolizumab Monotherapy in Patients With Lung Cancer

Study Overview
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Brief Summary
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The primary objective of the study is to compare the progression-free survival (PFS) of REGN2810 (cemiplimab) plus ipilimumab combination therapy (hereinafter referred to as REGN2810/ipi) and REGN2810 plus 2 cycles only of platinum-based doublet chemotherapy plus ipilimumab combination therapy (hereinafter referred to as REGN2810/chemo/ipi) with standard-of-care pembrolizumab monotherapy in the first-line treatment of patients with advanced squamous or non-squamous non-small cell lung cancer (NSCLC) whose tumors express programmed death ligand 1 (PD-L1) in ≥50% of tumor cells. The key secondary objectives of the study are to compare the overall survival (OS) of REGN2810/ipi and REGN2810/chemo/ipi with pembrolizumab monotherapy in the first-line treatment of patients with advanced squamous or non-squamous NSCLC whose tumors express PD-L1 in ≥50% of tumor cells and to compare the overall response rate (ORR) of REGN2810/ipi and REGN2810/chemo/ipi with pembrolizumab monotherapy in the first-line treatment of patients with advanced squamous or non-squamous NSCLC whose tumors express PD-L1 in ≥50% of tumor cells.

Official Title
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A Randomized, Phase 3, Open-Label Study of Combinations of REGN2810 (Anti-PD-1 Antibody), Platinum-based Doublet Chemotherapy, and Ipilimumab (Anti-CTLA-4 Antibody) Versus Pembrolizumab Monotherapy in First-Line Treatment of Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With Tumors Expressing PD-L1 ≥50%

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: REGN2810/ipi
* Drug: REGN2810/chemo/ipi
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patients with histologically or cytologically documented squamous or non-squamous NSCLC with stage IIIB or stage IV disease, who received no prior systemic treatment for recurrent or metastatic NSCLC Availability of an archival (≤5 months) or on-study obtained formalin-fixed, paraffin-embedded tumor tissue sample which has not previously been irradiated Expression of PD-L1 in ≥50% of tumor cells determined by the commercially available assay performed by the central laboratory At least 1 radiographically measureable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 Anticipated life expectancy of at least 3 months Key Exclusion Criteria: Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime Active or untreated brain metastases or spinal cord compression Patients with tumors tested positive for Epidermal growth factor receptor (EGFR) gene mutations, Anaplastic lymphoma kinase (ALK) gene translocations, or C-ros oncogene receptor tyrosine kinase(ROS1) fusions Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk of immune-related treatment-emergent adverse events (irTEAEs) Previous treatment with idelalisib at any time (ZYDELIG®) Patients with a condition requiring corticosteroid therapy (>10 mg prednisone/day or equivalent) within 14 days of randomization Note: Other protocol defined Inclusion/Exclusion criteria may 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 |
| --- | --- |
| Active Comparator: Pembrolizumab<br>Pembrolizumab | Drug: Pembrolizumab<br>* Reference drug administered IV infusion<br>|
| Experimental: REGN2810/ipi<br>REGN2810/ipi | Drug: REGN2810/ipi<br>* REGN2810 plus ipilimumab<br>* Other names: cemiplimab;|
| Experimental: REGN2810/chemo/ipi<br>REGN2810/chemo/ipi | Drug: REGN2810/chemo/ipi<br>* REGN2810 plus chemotherapy plus Ipilimumab<br>* Other names: cemiplimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessments | Per protocol, the final analysis of PFS was to be performed after observing 142 PFS events in the pembrolizumab treatment arm. PFS was not assessed due to insufficient data collected. | Up to 32 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Per protocol, if the final analysis of PFS was statistically significant for both cemiplimab combination therapy versus pembrolizumab treatment, the analysis of OS for cemiplimab combinations-versus-pembrolizumab comparison was to be performed at the time of PFS analysis, 12 months, and 18 months after analysis of PFS using the same method as used in the analysis of PFS. | Up to 32 months | 
| Objective Response Rate (ORR) | Per protocol, the ORR for each cemiplimab combination-versus-pembrolizumab comparison was to be analyzed using the Cochran-Mantel-Haenszel test stratified by histological status (non-squamous versus squamous). | Up to 32 months | 
| Number of Treatment-Emergent Adverse Events (TEAEs) |  | Up to 32 months | 
| Number of Participants With Dose-Limiting Toxicities (DLTs) |  | Up to 32 months | 
| Number of Participants With Any Serious TEAEs |  | Up to 32 months | 
| Number of Participants With TEAEs Leading to Death |  | Up to 32 months | 
| Number of Participants With Laboratory Abnormalities |  | Up to 32 months | 
| Overall Survival (OS) at 12 Months | Per protocol, if the final analysis of PFS was statistically significant for both cemiplimab combination therapy versus pembrolizumab treatment, the analysis of OS for cemiplimab combinations-versus-pembrolizumab comparison was to be performed at the time of PFS analysis, 12 months, and 18 months after analysis of PFS using the same method as used in the analysis of PFS. | At 12 months | 
| Overall Survival (OS) at 18 Months | Per protocol, if the final analysis of PFS was statistically significant for both cemiplimab combination therapy versus pembrolizumab treatment, the analysis of OS for cemiplimab combinations-versus-pembrolizumab comparison was to be performed at the time of PFS analysis, 12 months, and 18 months after analysis of PFS using the same method as used in the analysis of PFS. | At 18 months | 
| Quality of Life (Core 30 Questionnaire) | Quality of Life (QoL) as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) four-point scale, with 1 as not at all and 4 as very much. Per protocol, the change in EORTC QLQ-C30 scores from the first assessment to the end of the study were to be summarized descriptively at each post-baseline time point and compared using a mixed effects model, if appropriate. | Up to 32 months | 
| Quality of Life (Lung Cancer 13 Questionnaire) | QoL as measured by the Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) to assess lung cancer-associated symptoms and treatment-related side effects among lung cancer patients. The scale for EORTC-QLQ-LC13 is 1-4 for most outcome measures of systems, with 1 rated as not at all and 4 rated as very much. Per protocol, the change in EORTC QLQ-LC13 scores from the first assessment to the end of the study were to be summarized descriptively at each post-baseline time point and compared using a mixed effects model, if appropriate. | Up to 32 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stage IIIB, Stage IV, Non-squamous NSCLC, Squamous NSCLC