Combinations of Cemiplimab (Anti-PD-1 Antibody) and Platinum-based Doublet Chemotherapy in Patients With Lung Cancer

Study Overview
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Brief Summary
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The primary objectives of this study are: Part 1: To compare the overall survival (OS) of cemiplimab/chemo-f and cemiplimab/chemo-l/ipi versus platinum-based doublet chemotherapy in the first-line treatment of patients with advanced squamous or nonsquamous non-small cell lung cancer (NSCLC) with tumors expressing PD-L1 in <50% of tumor cells. Part 2: To compare the OS of cemiplimab/chemo-f with placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression. The key secondary objectives are: Part 1: To compare the progression-free survival (PFS) and objective response rate (ORR) of cemiplimab/chemo-f and cemiplimab/chemo-l/ipi versus chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC and tumors expressing PD-L1 in <50% of tumor cells. Part 2: To compare the PFS and ORR of cemiplimab/chemo-f versus placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression.

Official Title
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A Two-Part Randomized, Phase 3 Study of Combinations of Cemiplimab (Anti-PD-1 Antibody) and Platinum-based Doublet Chemotherapy in First-line Treatment of Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: REGN2810
* Drug: REGN2810/chemo/ipi
* Other: Chemotherapy
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Men and women ≥20 years of age for Japanese patients Patients with histologically or cytologically documented squamous or non-squamous NSCLC with stage IIIB or IIIC disease who are not candidates for treatment with definitive concurrent chemoradiation or patients with stage IV disease if they have not received 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 from a metastatic or recurrent site, which has not previously been irradiated Part 1 only: Expression of PD-L1 in <50% of tumor cells determined by a commercially available assay performed by the central laboratory At least 1 radiographically measurable 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: Part 1 only: 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 enrollment 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) 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Chemo<br>Part 1: Chemotherapy | Other: Chemotherapy<br>* Platinum-based doublet chemotherapy Part 1<br>Drug: Placebo<br>* Matching placebo Part 2<br>|
| Experimental: REGN2810+Chemo Part 1<br>Part 1: REGN2810+chemo | Drug: REGN2810<br>* REGN2810 plus Platinum-based doublet chemotherapy Part 1 and Part 2<br>* Other names: cemiplimab;|
| Experimental: REGN2810+AbbrevChemo+ipi<br>Part 1: REGN2810+abbrev chemo+ipi | Drug: REGN2810/chemo/ipi<br>* REGN2810 plus abbreviated chemotherapy plus Ipilimumab Part 1<br>* Other names: cemiplimab;|
| Experimental: Placebo+Chemo<br>Part 2: Placebo plus chemo | Drug: Placebo<br>* Matching placebo Part 2<br>|
| Experimental: REGN2810+Chemo Part 2<br>Part 2: REGN2810+chemo | Drug: REGN2810<br>* REGN2810 plus Platinum-based doublet chemotherapy Part 1 and Part 2<br>* Other names: cemiplimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Up to 32 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Up to 32 months | 
| Objective response rate |  | Up to 32 months | 
| Duration of Response (DOR) |  | Up to 32 months | 
| Best overall response (BOR) |  | Up to 32 months | 
| Incidence of Treatment-emergent adverse events (TEAEs) |  | Up to 32 months | 
| Incidence of Dose-limiting toxicities (DLTs) | Part 1 only | Up to 32 months | 
| Incidence of serious adverse events (SAEs) |  | Up to 32 months | 
| Incidence of deaths |  | Up to 32 months | 
| Incidence of laboratory abnormalities |  | Up to 32 months | 
| Overall survival rate |  | 12 months | 
| Overall survival rate |  | 18 months | 
| Overall survival rate |  | 24 months | 
| Quality of life as measured by EORTC QLQ-C30 | European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Up to 32 months | 
| Quality of life as measured by EORTC QLQ-LC13 | Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) | 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 IIIC, Stage IV, Non-squamous NSCLC, Squamous NSCLC