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

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ClinicalTrials.gov Identifier: NCT03515629
Recruitment Status : Terminated (Business decision)
First Posted : May 3, 2018
Results First Posted : November 16, 2022
Last Update Posted : November 16, 2022
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

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

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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 : July 2, 2018
Actual Primary Completion Date : July 29, 2021
Actual Study Completion Date : July 29, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

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




Primary Outcome Measures :
  1. 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 [ Time Frame: Up to 32 months ]
    Per protocol, the final analysis of PFS was to be performed after observing 142 PFS events in the pembrolizumab treatment arm. PFS was not assessed due to insufficient data collected.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 32 months ]
    Per protocol, if the final analysis of PFS was statistically significant for both cemiplimab combination therapy versus pembrolizumab treatment, the analysis of OS for cemiplimab combinations-versus-pembrolizumab comparison was to be performed at the time of PFS analysis, 12 months, and 18 months after analysis of PFS using the same method as used in the analysis of PFS.

  2. Objective Response Rate (ORR) [ Time Frame: Up to 32 months ]
    Per protocol, the ORR for each cemiplimab combination-versus-pembrolizumab comparison was to be analyzed using the Cochran-Mantel-Haenszel test stratified by histological status (non-squamous versus squamous).

  3. Number of Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to 32 months ]
  4. Number of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to 32 months ]
  5. Number of Participants With Any Serious TEAEs [ Time Frame: Up to 32 months ]
  6. Number of Participants With TEAEs Leading to Death [ Time Frame: Up to 32 months ]
  7. Number of Participants With Laboratory Abnormalities [ Time Frame: Up to 32 months ]
  8. Overall Survival (OS) at 12 Months [ Time Frame: At 12 months ]
    Per protocol, if the final analysis of PFS was statistically significant for both cemiplimab combination therapy versus pembrolizumab treatment, the analysis of OS for cemiplimab combinations-versus-pembrolizumab comparison was to be performed at the time of PFS analysis, 12 months, and 18 months after analysis of PFS using the same method as used in the analysis of PFS.

  9. Overall Survival (OS) at 18 Months [ Time Frame: At 18 months ]
    Per protocol, if the final analysis of PFS was statistically significant for both cemiplimab combination therapy versus pembrolizumab treatment, the analysis of OS for cemiplimab combinations-versus-pembrolizumab comparison was to be performed at the time of PFS analysis, 12 months, and 18 months after analysis of PFS using the same method as used in the analysis of PFS.

  10. Quality of Life (Core 30 Questionnaire) [ Time Frame: Up to 32 months ]
    Quality of Life (QoL) 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." Per protocol, the change in EORTC QLQ-C30 scores from the first assessment to the end of the study were to be summarized descriptively at each post-baseline time point and compared using a mixed effects model, if appropriate.

  11. Quality of Life (Lung Cancer 13 Questionnaire) [ Time Frame: Up to 32 months ]
    QoL 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." Per protocol, the change in EORTC QLQ-LC13 scores from the first assessment to the end of the study were to be summarized descriptively at each post-baseline time point and compared using a mixed effects model, if appropriate.



Information from the National Library of Medicine

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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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03515629


Locations
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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
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Regeneron Pharmaceuticals:
Study Protocol  [PDF] May 14, 2018
Statistical Analysis Plan  [PDF] August 24, 2021

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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    Key Record Dates
Results First Posted: November 16, 2022
Last Update Posted: November 16, 2022
Last Verified: October 2022

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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:
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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