A Study of REGN2810 and Ipilimumab in Patients With Lung Cancer

Advanced Non-Small Cell Lung Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03430063
• Other study ID #: R2810-ONC-1763
• Secondary ID: 2017-003684-35
• Status: Terminated
• Phase: Phase 2
• Start date: May 29, 2018
• Est. completion date: October 27, 2021

Study information

• Verified date: October 2022
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: October 27, 2021
• Est. primary completion date: October 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Non-Small Cell Lung Carcinoma
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• SDREGN2810
Standard dose intravenous (IV) infusion
• SDREGN2810/ipi
Combination therapy dose IV
• HDREGN2810
High dose IV

Locations

Country	Name	City	State
Belgium	Regeneron Research Site	Herstal
Belgium	Regeneron Research Site	Yvoir
France	Regeneron Research Site	Poitiers
France	Regeneron Research Site	Rennes
France	Regeneron Research Site	Saint-Mandé
Germany	Regeneron Research Site	Gauting
Korea, Republic of	Regeneron Research Site	Incheon
Korea, Republic of	Regeneron Research Site	Jeongnam
Korea, Republic of	Regeneron Research Site	Seongnam
Korea, Republic of	Regeneron Research Site	Seoul
Korea, Republic of	Regeneron Research Site	Seoul
Korea, Republic of	Regeneron Research Site	Seoul
Korea, Republic of	Regeneron Research Site	Suwon
Poland	Regeneron Research Site	Gdynia
Poland	Regeneron Research Site	Grudziadz
Poland	Regeneron Research Site	Otwock
Spain	Regeneron Research Site	Badalona
Spain	Regeneron Research Site	Barcelona
Spain	Regeneron Research Site	Madrid
Spain	Regeneron Research Site	Málaga
Spain	Regeneron Research Site	Zaragoza
Taiwan	Regeneron Research Site	Taipei
United Kingdom	Regeneron Research Site	London
United Kingdom	Regeneron Research Site	Manchester
United Kingdom	Regeneron Research Site	Plymouth
United States	Regeneron Research Site	Canton	Ohio
United States	Regeneron Research Site	Los Angeles	California
United States	Regeneron Research Site	Massillon	Ohio
United States	Regeneron Research Site	Phoenix	Arizona
United States	Regeneron Research Site	Scarborough	Maine
United States	Regeneron Research Site	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Korea, Republic of,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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