A Study of REGN2810 and Ipilimumab 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 objective response rate (ORR) of high dose cemiplimab (HDREGN2810) and standard dose cemiplimab plus ipilimumab combination therapy (SDREGN2810/ipi) to the ORR of standard dose cemiplimab (SDREGN2810) in the second-line treatment of patients with advanced squamous or non-squamous non-small cell lung cancer (NSCLC), in patients whose tumors express programmed cell death ligand 1 (PD-L1) in <50% of tumor cells.

Official Title
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A Randomized, Open-Label Study of Combinations of Standard and High Dose REGN2810 (Cemiplimab; Anti-PD-1 Antibody) and Ipilimumab (Anti-CTLA-4 Antibody) in the Second-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Advanced Non-Small Cell Lung Carcinoma

Intervention / Treatment
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* Drug: SDREGN2810
* Drug: SDREGN2810/ipi
* Drug: HDREGN2810


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 who either have stage IIIb or stage IIIc disease who are not candidates for treatment with definitive concurrent chemo-radiation or have stage IV disease. Patients must have PD after receiving one prior line of chemotherapy treatment for advanced NSCLC. Availability of an archival or on-study obtained formalin-fixed, paraffin-embedded tumor tissue biopsy sample Biopsy evaluable for expression of PD-L1 as determined by a PD-L1 Immunohistochemistry (IHC) pharma diagnostic test (pharmDx) assay performed by a central laboratory At least 1 radiographically measureable lesion by computed tomography (CT) per RECIST 1.1 criteria Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 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 randomization History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), or 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 a risk of immunerelated treatment-emergent adverse events (irTEAEs) 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 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: SDREGN2810<br> | Drug: SDREGN2810<br>* Standard dose intravenous (IV) infusion<br>* Other names: cemiplimab;|
| Experimental: SDREGN2810/ipi<br> | Drug: SDREGN2810/ipi<br>* Combination therapy dose IV<br>* Other names: ipilimumab;|
| Experimental: HDREGN2810<br> | Drug: HDREGN2810<br>* High dose IV<br>* Other names: cemiplimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) in Participants Whose Tumors Express Programmed Cell Death Ligand 1 (PD-L1) in <50% of Tumor Cells | ORR was defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of participants in the efficacy analysis set. BOR was defined as the best response recorded, as determined by a blinded Independent Review Committee (IRC) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) between the date of randomization and the date of the first objectively documented progression or the date of subsequent anti-cancer therapy, whichever came first. CR was defined as the disappearance of all target lesions (Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm [<1 cm]). PR was defined as having at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. | From date of randomization up to 41 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall Response Rate was defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of participants in the efficacy analysis set. BOR was defined as the best response recorded, as determined by a blinded Independent Review Committee (IRC) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) between the date of randomization and the date of the first objectively documented progression or the date of subsequent anti-cancer therapy, whichever came first. CR was defined as the disappearance of all target lesions (Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm [<1 cm]). PR was defined as having at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. | From date of randomization up to 41 months | 
| Overall Survival (OS) in Participants With Tumor PD-L1 Expression Levels <50% of Tumor Cells | OS was defined as the time from randomization to the date of death due to any cause. A participant who lost to follow-up was censored at the last date that the participant was known to be alive. OS was measured using Kaplan-Meier method. | Time from randomization to the date of death (up to 41 months) | 
| Progression Free Survival (PFS) in Participants With Tumor PD-L1 Expression Levels <50% of Tumor Cells | PFS was defined as the time from randomization to the date of the first documented tumor progression, as determined by the IRC (based on RECIST 1.1 assessments) or death due to any cause, whichever occurred earlier. PFS was measured using Kaplan-Meier method. | Time from randomization up to the date of the first documented tumor progression or death (up to 41 months) | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Resulting in Death | Adverse event (AE): any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Number of participants with TEAEs, Serious TEAEs and TEAEs leading to death were reported. | Up to 41 months | 
| Number of Participants With Laboratory Test Abnormalities of Grade 2 or Higher Severity Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grading System | The laboratory measurements included hematology, chemistry, electrolytes and liver function. NCI-CTCAE was graded according to the following scale: Grade 1 (Mild): Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 (Moderate): Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL); Grade 3 (Severe): Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4 (Life-threatening): Life-threatening consequences; urgent intervention indicated; Grade 5 (Death): Death related to AE. | Up to 41 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced non-squamous NSCLC, Advanced squamous NSCLC