Non-small Cell Lung Cancer
Conditions
Keywords
Stage IIIB, Stage IV, Non-squamous NSCLC, Squamous NSCLC
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.
Interventions
DRUGREGN2810/ipi
REGN2810 plus ipilimumab
REGN2810 plus chemotherapy plus Ipilimumab
DRUGPembrolizumab
Reference drug administered IV infusion
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 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. |
| Objective Response Rate (ORR) | 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). |
| Number of Treatment-Emergent Adverse Events (TEAEs) | Up to 32 months | — |
| Number of Participants With Dose-Limiting Toxicities (DLTs) | Up to 32 months | — |
| Number of Participants With Any Serious TEAEs | Up to 32 months | — |
| Number of Participants With TEAEs Leading to Death | Up to 32 months | — |
| Number of Participants With Laboratory Abnormalities | Up to 32 months | — |
| Overall Survival (OS) at 12 Months | 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. |
| Overall Survival (OS) at 18 Months | 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. |
| Quality of Life (Core 30 Questionnaire) | 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. |
| Quality of Life (Lung Cancer 13 Questionnaire) | 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. |
Countries
Italy, Lithuania, United States
Participant flow
Recruitment details
This study was conducted at 3 centers that randomized 5 participants in the United States, Lithuania, and Italy.
Pre-assignment details
Due to program de-prioritization, the sponsor decided to cease enrollment at which time only 5 participants were randomized to 2 of 3 treatment arms (i.e., no participants were randomized to receive pembrolizumab).
Participants by arm
| Arm | Count |
|---|---|
| Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an intravenous (IV) infusion every 3 weeks (Q3W) for 108 weeks in combination with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses. | 3 |
| Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W Cemiplimab was administered at 350 mg as an IV infusion Q3W for 108 weeks in combination with platinum-based doublet chemotherapy administered IV Q3W for 2 cycles and with ipilimumab administered IV over approximately 90 minutes at 50 mg Q6W for up to 4 doses. | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 1 |
| Overall Study | Progressive disease | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Cemiplimab 350 mg Q3W + Chemotherapy + Ipilimumab 50 mg Q6W | Total | Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W |
|---|---|---|---|
| Age, Continuous | 56.5 Years STANDARD_DEVIATION 4.95 | 59.6 Years STANDARD_DEVIATION 7.57 | 61.7 Years STANDARD_DEVIATION 9.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 1 / 2 |
| other Total, other adverse events | 3 / 3 | 2 / 2 |
| serious Total, serious adverse events | 2 / 3 | 2 / 2 |
Outcome results
Primary
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
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.
Time frame: Up to 32 months
Population: PFS was not assessed due to insufficient data collected.
Secondary
Number of Participants With Any Serious TEAEs
Time frame: Up to 32 months
Population: Safety analysis set (SAF), defined as all enrolled participants who received any amount of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants With Any Serious TEAEs | 2 Participants |
| Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W | Number of Participants With Any Serious TEAEs | 2 Participants |
Secondary
Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Up to 32 months
Population: Safety analysis set (SAF), defined as all enrolled participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities
Time frame: Up to 32 months
Population: Safety analysis set (SAF), defined as all enrolled participants who received any amount of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants With Laboratory Abnormalities | 1 Participants |
| Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W | Number of Participants With Laboratory Abnormalities | 1 Participants |
Secondary
Number of Participants With TEAEs Leading to Death
Time frame: Up to 32 months
Population: Safety analysis set (SAF), defined as all enrolled participants who received any amount of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants With TEAEs Leading to Death | 1 Participants |
| Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W | Number of Participants With TEAEs Leading to Death | 0 Participants |
Secondary
Number of Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to 32 months
Population: Safety analysis set (SAF), defined as all enrolled participants who received any amount of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Number of Treatment-Emergent Adverse Events (TEAEs) | 68 Events |
| Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W | Number of Treatment-Emergent Adverse Events (TEAEs) | 91 Events |
Secondary
Objective Response Rate (ORR)
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).
Time frame: Up to 32 months
Population: ORR was not assessed due to insufficient data collected.
Secondary
Overall Survival (OS)
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.
Time frame: Up to 32 months
Population: OS was not assessed due to insufficient data collected.
Secondary
Overall Survival (OS) 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.
Time frame: At 12 months
Population: OS was not assessed due to insufficient data collected.
Secondary
Overall Survival (OS) 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.
Time frame: At 18 months
Population: OS was not assessed due to insufficient data collected.
Secondary
Quality of Life (Core 30 Questionnaire)
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.
Time frame: Up to 32 months
Population: Due to the minimal amount of responses and decrease in number of overall participants analyzed for this outcome measure, results are not reported to protect the confidentiality of the participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pembrolizumab | Quality of Life (Core 30 Questionnaire) | NA Score on a scale |
| Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W | Quality of Life (Core 30 Questionnaire) | NA Score on a scale |
Secondary
Quality of Life (Lung Cancer 13 Questionnaire)
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.
Time frame: Up to 32 months
Population: Due to the minimal amount of responses and decrease in number of overall participants analyzed for this outcome measure, results are not reported to protect the confidentiality of the participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Quality of Life (Lung Cancer 13 Questionnaire) | NA Score on a scale |
| Cemiplimab 350 mg Q3W + Ipilimumab 50 mg Q6W | Quality of Life (Lung Cancer 13 Questionnaire) | NA Score on a scale |