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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03430063

Enrollment

Registered

2018-02-12

Start date

2018-05-29

Completion date

2021-10-27

Last updated

2022-11-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Non-Small Cell Lung Carcinoma

Keywords

Advanced non-squamous NSCLC, Advanced squamous NSCLC

Brief 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.

Interventions

DRUGSDREGN2810

Standard dose intravenous (IV) infusion

DRUGSDREGN2810/ipi

Combination therapy dose IV

DRUGHDREGN2810

High dose IV

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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/

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate (ORR) in Participants Whose Tumors Express Programmed Cell Death Ligand 1 (PD-L1) in <50% of Tumor Cells	From date of randomization up to 41 months	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.

Secondary

Measure	Time frame	Description
Overall Response Rate	From date of randomization up to 41 months	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.
Overall Survival (OS) in Participants With Tumor PD-L1 Expression Levels <50% of Tumor Cells	Time from randomization to the date of death (up to 41 months)	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.
Progression Free Survival (PFS) in Participants With Tumor PD-L1 Expression Levels <50% of Tumor Cells	Time from randomization up to the date of the first documented tumor progression or death (up to 41 months)	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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Resulting in Death	Up to 41 months	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.
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	Up to 41 months	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.

Countries

Belgium, France, Germany, Poland, South Korea, Spain, Taiwan, United Kingdom, United States

Participant flow

Recruitment details

Due to early enrollment cessation, only 28 participants were randomized and 27 participants received study treatment in this study. One participant was randomized but not treated.

Pre-assignment details

Of the 27 participants treated, four participants completed the study. The most common reason for study discontinuation was death (8 participants) followed by withdrawal of consent (6 participants), and progressive disease (4 participants).

Participants by arm

Arm	Count
Cemiplimab 350 mg Q3W Participants received 350 mg of cemiplimab IV infusion on Day 1 of Q3W for up to 108 weeks or until progression of disease or unacceptable toxicity, withdrawal of consent, death, initiation of another anti-cancer treatment.	8
Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W Participants received 350 mg of cemiplimab IV infusion on Day 1 of Q3W for up to 108 weeks followed by ipilimumab 50 mg flat dose administered IV on Day 1 of every other treatment cycle (every 42 days or every 6 weeks \[Q6W\]) for up to 4 doses or until progression of disease or unacceptable toxicity, withdrawal of consent, death, initiation of another anti-cancer treatment.	11
Cemiplimab 1050 mg Q3W Participants received 1050 mg of cemiplimab IV infusion on Day 1 of Q3W for up to 108 weeks or until progression of disease or unacceptable toxicity, withdrawal of consent, death, initiation of another anti-cancer treatment.	8
Total	27

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	0	1	0
Overall Study	Death	3	2	3
Overall Study	Lost to Follow-up	0	1	0
Overall Study	Other un-specified	1	1	0
Overall Study	Progressive disease	1	2	1
Overall Study	Randomized, but never treated	0	0	1
Overall Study	Withdrawal by Subject	0	0	1
Overall Study	Withdrawal of consent	3	1	2

Baseline characteristics

Characteristic	Cemiplimab 350 mg Q3W	Total	Cemiplimab 1050 mg Q3W	Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W
Age, Continuous	62.4 years STANDARD_DEVIATION 7.91	66.6 years STANDARD_DEVIATION 9.65	68.1 years STANDARD_DEVIATION 12.08	68.5 years STANDARD_DEVIATION 8.72
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants	19 Participants	6 Participants	7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants	8 Participants	2 Participants	4 Participants
Number of Participants with PD-L1 Tumor Expression Levels of ≥50% of Tumor Cells	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	6 Participants	12 Participants	3 Participants	3 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	7 Participants	2 Participants	3 Participants
Race (NIH/OMB) White	0 Participants	8 Participants	3 Participants	5 Participants
Sex: Female, Male Female	2 Participants	7 Participants	1 Participants	4 Participants
Sex: Female, Male Male	6 Participants	20 Participants	7 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	3 / 8	3 / 11	4 / 8
other Total, other adverse events	7 / 8	11 / 11	8 / 8
serious Total, serious adverse events	1 / 8	7 / 11	4 / 8

Outcome results

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.

Time frame: From date of randomization up to 41 months