REGN2810 (Anti-PD-1 Antibody), Platinum-based Doublet Chemotherapy, and Ipilimumab (Anti-CTLA-4 Antibody) Versus Pembrolizumab Monotherapy in Patients With Lung Cancer
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: REGN2810/ipi; REGN2810/chemo/ipi; Pembrolizumab
Intervention description: REGN2810 plus ipilimumab; REGN2810 plus chemotherapy plus Ipilimumab; Reference drug administered IV infusion
Intervention MeSH terms: Pembrolizumab; Cemiplimab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stage IIIB; Stage IV; Non-squamous NSCLC; Squamous NSCLC

Summary:

      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.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. 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

          2. Availability of an archival (≤5 months) or on-study obtained formalin-fixed,
             paraffin-embedded tumor tissue sample which has not previously been irradiated

          3. Expression of PD-L1 in ≥50% of tumor cells determined by the commercially available
             assay performed by the central laboratory

          4. 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

          5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1

          6. Anticipated life expectancy of at least 3 months

        Key Exclusion Criteria:

          1. Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime

          2. Active or untreated brain metastases or spinal cord compression

          3. 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

          4. Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed
             consent

          5. 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

          6. 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)

          7. Previous treatment with idelalisib at any time (ZYDELIG®)

          8. 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