Clinical trial NCT03515629: REGN2810 (Anti-PD-1 Antibody), Platinum-based Doublet Chemotherapy, and Ipilimumab (Anti-CTLA-4 Antibody) Versus Pembrolizumab Monotherapy in Patients With Lung Cancer
Official title: 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%
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Keywords: Stage IIIB
Stage IV
Non-squamous NSCLC
Squamous NSCLC
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2018-05-03
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: 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
timeFrame: Up to 32 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 32 months
measure: Objective Response Rate (ORR)
timeFrame: Up to 32 months
measure: Number of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 32 months
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Up to 32 months
measure: Number of Participants With Any Serious TEAEs
timeFrame: Up to 32 months
measure: Number of Participants With TEAEs Leading to Death
timeFrame: Up to 32 months
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Up to 32 months
measure: Overall Survival (OS) at 12 Months
timeFrame: At 12 months
measure: Overall Survival (OS) at 18 Months
timeFrame: At 18 months
measure: Quality of Life (Core 30 Questionnaire)
timeFrame: Up to 32 months
measure: Quality of Life (Lung Cancer 13 Questionnaire)
timeFrame: Up to 32 months
Other outcomes:
Locations:
city: Saint Petersburg
country: United States
facility: Regeneron Research Site
state: Florida
city: Cremona
country: Italy
facility: Regeneron Research Site
city: Vilnius
country: Lithuania
facility: Regeneron Research Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: