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

• ClinicalTrials.gov Identifier: NCT03515629
• Recruitment Status: Completed
• First Posted: May 3, 2018
• Last Update Posted: August 13, 2021
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: REGN2810/ipi; Drug: REGN2810/chemo/ipi; Drug: Pembrolizumab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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%
• Actual Study Start Date: June 4, 2018
• Actual Primary Completion Date: July 29, 2021
• Actual Study Completion Date: July 29, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Pembrolizumab; Pembrolizumab	Drug: Pembrolizumab; Reference drug administered IV infusion
Experimental: REGN2810/ipi; REGN2810/ipi	Drug: REGN2810/ipi; REGN2810 plus ipilimumab; Other Name: cemiplimab
Experimental: REGN2810/chemo/ipi; REGN2810/chemo/ipi	Drug: REGN2810/chemo/ipi; REGN2810 plus chemotherapy plus Ipilimumab; Other Name: cemiplimab

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Up to 32 months ]

Secondary Outcome Measures :

1. Overall survival (OS) [ Time Frame: Up to 32 months ]
2. Objective response rate (ORR) [ Time Frame: Up to 32 months ]
3. Incidence of Treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 32 months ]
4. Incidence of Dose-limiting toxicities (DLTs) [ Time Frame: Up to 32 months ]
5. Incidence of serious adverse events (SAEs) [ Time Frame: Up to 32 months ]
6. Incidence of deaths [ Time Frame: Up to 32 months ]
7. Incidence of laboratory abnormalities [ Time Frame: Up to 32 months ]
8. Overall survival [ Time Frame: 12 months ]
9. Overall survival [ Time Frame: 18 months ]
10. Quality of life (Core 30 Questionnaire) [ Time Frame: Up to 32 months ]
    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"
11. Quality of life (Lung Cancer 13 Questionnaire) [ Time Frame: Up to 32 months ]
    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".

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Florida

Regeneron Research Site

Saint Petersburg, Florida, United States, 33709

Italy

Regeneron Research Site

Cremona, Italy, 26100

Lithuania

Regeneron Research Site

Vilnius, Lithuania, 08660

Sponsors and Collaborators

Regeneron Pharmaceuticals

Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03515629
• Other Study ID Numbers: R2810-ONC-16111; 2017-001041-27 ( EudraCT Number )
• First Posted: May 3, 2018
• Last Update Posted: August 13, 2021
• Last Verified: August 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Regeneron Pharmaceuticals:

Stage IIIB; Stage IV; Non-squamous NSCLC; Squamous NSCLC

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pembrolizumab; Cemiplimab; Antineoplastic Agents, Immunological; Antineoplastic Agents