A Study of REGN2810 and Ipilimumab in Patients With Lung Cancer

A Randomized, Open-Label Study of Combinations of Standard and High Dose REGN2810 (Cemiplimab; Anti-PD-1 Antibody) and Ipilimumab (Anti-CTLA-4 Antibody) in the Second-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer

The primary objective of the study is to compare the objective response rate (ORR) of high dose cemiplimab (HDREGN2810) and standard dose cemiplimab plus ipilimumab combination therapy (SDREGN2810/ipi) to the ORR of standard dose cemiplimab (SDREGN2810) in the second-line treatment of patients with advanced squamous or non-squamous non-small cell lung cancer (NSCLC), in patients whose tumors express programmed cell death ligand 1 (PD-L1) in <50% of tumor cells.

Study Overview

• Status: Terminated
• Conditions: Advanced Non-Small Cell Lung Carcinoma
• Intervention / Treatment: Drug: SDREGN2810; Drug: SDREGN2810/ipi; Drug: HDREGN2810

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Herstal, Belgium, 4040
    • Regeneron Research Site
  • Yvoir, Belgium, 5530
    • Regeneron Research Site
• France
  • Poitiers, France, 86021
    • Regeneron Research Site
  • Rennes, France, 35033
    • Regeneron Research Site
  • Saint-Mandé, France, 94160
    • Regeneron Research Site
• Germany
  • Gauting, Germany, 82131
    • Regeneron Research Site
• Korea, Republic of
  • Incheon, Korea, Republic of, 22332
    • Regeneron Research Site
  • Jeongnam, Korea, Republic of, 58128
    • Regeneron Research Site
  • Seongnam, Korea, Republic of, 463707
    • Regeneron Research Site
  • Seoul, Korea, Republic of, 03722
    • Regeneron Research Site
  • Seoul, Korea, Republic of, 05505
    • Regeneron Research Site
  • Seoul, Korea, Republic of, 06591
    • Regeneron Research Site
  • Suwon, Korea, Republic of, 16247
    • Regeneron Research Site
• Poland
  • Gdynia, Poland, 81519
    • Regeneron Research Site
  • Grudziądz, Poland, 86300
    • Regeneron Research Site
  • Otwock, Poland, 05400
    • Regeneron Research Site
• Spain
  • Badalona, Spain, 8911
    • Regeneron Research Site
  • Barcelona, Spain, 08025
    • Regeneron Research Site
  • Madrid, Spain, 28046
    • Regeneron Research Site
  • Málaga, Spain, 29010
    • Regeneron Research Site
  • Zaragoza, Spain, 50009
    • Regeneron Research Site
• Taiwan
  • Taipei, Taiwan, 11217
    • Regeneron Research Site
• United Kingdom
  • London, United Kingdom, W1G6AD
    • Regeneron Research Site
  • Manchester, United Kingdom, M20 4BX
    • Regeneron Research Site
  • Plymouth, United Kingdom, PL68DH
    • Regeneron Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Regeneron Research Site
  • California
    • Los Angeles, California, United States, 90033
      • Regeneron Research Site
    • Whittier, California, United States, 90603
      • Regeneron Research Site
  • Maine
    • Scarborough, Maine, United States, 04074
      • Regeneron Research Site
  • Ohio
    • Canton, Ohio, United States, 44708
      • Regeneron Research Site
    • Massillon, Ohio, United States, 44646
      • Regeneron Research Site

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Patients with histologically or cytologically documented squamous or non-squamous NSCLC who either have stage IIIb or stage IIIc disease who are not candidates for treatment with definitive concurrent chemo-radiation or have stage IV disease. Patients must have PD after receiving one prior line of chemotherapy treatment for advanced NSCLC.
2. Availability of an archival or on-study obtained formalin-fixed, paraffin-embedded tumor tissue biopsy sample
3. Biopsy evaluable for expression of PD-L1 as determined by a PD-L1 Immunohistochemistry (IHC) pharma diagnostic test (pharmDx) assay performed by a central laboratory
4. At least 1 radiographically measureable lesion by computed tomography (CT) per RECIST 1.1 criteria
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1

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 randomization
5. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), or 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 a risk of immunerelated treatment-emergent adverse events (irTEAEs)
7. 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 apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SDREGN2810	Drug: SDREGN2810; Standard dose intravenous (IV) infusion; Other Names: REGN2810; cemiplimab
Experimental: SDREGN2810/ipi	Drug: SDREGN2810/ipi; Combination therapy dose IV; Other Names: ipilimumab; REGN2810; cemiplimab
Experimental: HDREGN2810	Drug: HDREGN2810; High dose IV; Other Names: REGN2810; cemiplimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) in Participants Whose Tumors Express Programmed Cell Death Ligand 1 (PD-L1) in <50% of Tumor Cells	ORR was defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of participants in the efficacy analysis set. BOR was defined as the best response recorded, as determined by a blinded Independent Review Committee (IRC) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) between the date of randomization and the date of the first objectively documented progression or the date of subsequent anti-cancer therapy, whichever came first. CR was defined as the disappearance of all target lesions (Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm [<1 cm]). PR was defined as having at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	From date of randomization up to 41 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall Response Rate was defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of participants in the efficacy analysis set. BOR was defined as the best response recorded, as determined by a blinded Independent Review Committee (IRC) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) between the date of randomization and the date of the first objectively documented progression or the date of subsequent anti-cancer therapy, whichever came first. CR was defined as the disappearance of all target lesions (Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm [<1 cm]). PR was defined as having at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	From date of randomization up to 41 months
Overall Survival (OS) in Participants With Tumor PD-L1 Expression Levels <50% of Tumor Cells	OS was defined as the time from randomization to the date of death due to any cause. A participant who lost to follow-up was censored at the last date that the participant was known to be alive. OS was measured using Kaplan-Meier method.	Time from randomization to the date of death (up to 41 months)
Progression Free Survival (PFS) in Participants With Tumor PD-L1 Expression Levels <50% of Tumor Cells	PFS was defined as the time from randomization to the date of the first documented tumor progression, as determined by the IRC (based on RECIST 1.1 assessments) or death due to any cause, whichever occurred earlier. PFS was measured using Kaplan-Meier method.	Time from randomization up to the date of the first documented tumor progression or death (up to 41 months)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Resulting in Death	Adverse event (AE): any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Number of participants with TEAEs, Serious TEAEs and TEAEs leading to death were reported.	Up to 41 months
Number of Participants With Laboratory Test Abnormalities of Grade 2 or Higher Severity Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grading System	The laboratory measurements included hematology, chemistry, electrolytes and liver function. NCI-CTCAE was graded according to the following scale: Grade 1 (Mild): Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 (Moderate): Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL); Grade 3 (Severe): Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4 (Life-threatening): Life-threatening consequences; urgent intervention indicated; Grade 5 (Death): Death related to AE.	Up to 41 months

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2018
• Primary Completion (Actual): October 27, 2021
• Study Completion (Actual): October 27, 2021

Study Registration Dates

• First Submitted: January 29, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (Actual): February 12, 2018

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Advanced non-squamous NSCLC; Advanced squamous NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab; Cemiplimab
• Other Study ID Numbers: R2810-ONC-1763; 2017-003684-35 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No