Non-small Cell Lung Cancer
Conditions
Keywords
Stage IIIB, Stage IIIC, Stage IV, Non-squamous NSCLC, Squamous NSCLC
Brief summary
The primary objectives of this study are: Part 1: To compare the overall survival (OS) of cemiplimab/chemo-f and cemiplimab/chemo-l/ipi versus platinum-based doublet chemotherapy in the first-line treatment of patients with advanced squamous or nonsquamous non-small cell lung cancer (NSCLC) with tumors expressing PD-L1 in \<50% of tumor cells. Part 2: To compare the OS of cemiplimab/chemo-f with placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression. The key secondary objectives are: Part 1: To compare the progression-free survival (PFS) and objective response rate (ORR) of cemiplimab/chemo-f and cemiplimab/chemo-l/ipi versus chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC and tumors expressing PD-L1 in \<50% of tumor cells. Part 2: To compare the PFS and ORR of cemiplimab/chemo-f versus placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression.
Interventions
DRUGREGN2810
REGN2810 plus Platinum-based doublet chemotherapy Part 1 and Part 2
REGN2810 plus abbreviated chemotherapy plus Ipilimumab Part 1
OTHERChemotherapy
Platinum-based doublet chemotherapy Part 1
DRUGPlacebo
Matching placebo Part 2
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part 1: Open label Part 2: Double blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Men and women ≥20 years of age for Japanese patients 2. Patients with histologically or cytologically documented squamous or non-squamous NSCLC with stage IIIB or IIIC disease who are not candidates for treatment with definitive concurrent chemoradiation or patients with stage IV disease if they have not received prior systemic treatment for recurrent or metastatic NSCLC 3. Availability of an archival (≤5 months) or on-study obtained formalin-fixed, paraffin-embedded tumor tissue sample from a metastatic or recurrent site, which has not previously been irradiated 4. Part 1 only: Expression of PD-L1 in \<50% of tumor cells determined by a commercially available assay performed by the central laboratory 5. At least 1 radiographically measurable 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 6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 7. Anticipated life expectancy of at least 3 months Key
Exclusion criteria
1. Part 1 only: 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 enrollment 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. 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 |
|---|---|---|
| Part 1: Overall Survival (OS) | Up to a maximum of 82.2 months | OS was defined as the time from randomization to the date of death due to any cause. |
| Part 2: OS | Up to a maximum of 68.4 months | OS was defined as the time from randomization to the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Progression-free Survival (PFS) Per Independent Review Committee (IRC) | Up to a maximum of 82.2 months | PFS as assessed by IRC per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was defined as the time from randomization to the date of the first documented tumor progression, or death due to any cause, whichever occurred earlier. |
| Part 2: PFS Per IRC | Up to a maximum of 68.4 months | PFS as assessed by IRC per RECIST 1.1 was defined as the time from randomization to the date of the first documented tumor progression, or death due to any cause, whichever occurred earlier. |
| Part 1: Objective Response Rate (ORR) Per IRC | Up to 32 months | ORR as assessed by IRC per RECIST 1.1 was defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR). |
| Part 2: ORR Per IRC | Up to 32 months | ORR as assessed by IRC per RECIST 1.1 was defined as the percentage of participants with a BOR of confirmed CR or PR. |
| Part 1: Duration of Response (DoR) | Up to 32 months | DoR was defined as the time from date of first documented response of CR or PR to the date of first documented progressive disease (PD) or death due to any cause, whichever occurred earlier. |
| Part 2: DoR | Up to 32 months | DoR was defined as the time from date of first documented response of CR or PR to the date of first documented PD or death due to any cause, whichever occurred earlier. |
| Part 1: Best Overall Response (BOR) Per IRC | Up to 32 months | BOR was defined as the best overall response as determined by the IRC per RECIST 1.1, between the date of randomization and the date of first documented tumor progression or the date of subsequent anti-cancer therapy, whichever occurred earlier. |
| Part 2: BOR Per IRC | Up to 32 months | BOR was defined as the best overall response as determined by the IRC per RECIST 1.1, between the date of randomization and the date of first documented tumor progression or the date of subsequent anti-cancer therapy, whichever occurred earlier. |
| Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug in Part 1, up to approximately 83 months | TEAEs were AEs that developed or worsened during the on-treatment period and any treatment-related AEs that occurred during the post-treatment period but prior to start of another anti-cancer systemic therapy. |
| Part 2: Number of Participants With TEAEs | From first dose of study drug in Part 2, up to approximately 69 months | TEAEs were AEs that developed or worsened during the on-treatment period and any treatment-related AEs that occurred during the post-treatment period but prior to start of another anti-cancer systemic therapy. |
| Part 1: Number of Participants With Dose-limiting Toxicities (DLTs) | 28 days | Part 1 only |
| Part 1: Number of Participants With Serious TEAEs | From first dose of study drug in Part 1, up to approximately 83 months | Serious TEAEs were defined as medically significant but not immediately life-threatening AEs that developed or worsened during the on-treatment period and any treatment-related AEs that occurred during the post-treatment period but prior to start of another anti-cancer systemic therapy. |
| Part 2: Number of Participants With Serious TEAEs | From first dose of study drug in Part 2, up to approximately 69 months | Serious TEAEs were defined as medically significant but not immediately life-threatening AEs that developed or worsened during the on-treatment period and any treatment-related AEs that occurred during the post-treatment period but prior to start of another anti-cancer systemic therapy. |
| Part 1: Number of Deaths During the On-Treatment Period | Up to 28 months | The on-treatment period was defined as the day from the first dose of study drug to the day of the last dose of study drug plus 90 days or 1 day before participants receive their first dose of new anti-cancer systemic therapy, whichever is earlier. |
| Part 2: Number of Deaths During the On-Treatment Period | Up to 28 months | The on-treatment period was defined as the day from the first dose of study drug to the day of the last dose of study drug plus 90 days or 1 day before participants receive their first dose of new anti-cancer systemic therapy, whichever is earlier. |
| Part 1: Estimated Survival Probability | 12 months, 18 months, 24 months | OS rate at a landmark (12, 18, and 24 months) was defined as the Kaplan-Meier (K-M) estimated probability of participants who survived due to any cause at the landmark after randomization. |
| Part 2: Estimated Survival Probability | 12 months, 18 months, 24 months | OS rate at a landmark (12, 18, and 24 months) was defined as the K-M estimated probability of participants who survived due to any cause at the landmark after randomization. |
| Part 1: Change From Baseline in Global Health Status Score as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Baseline, Day 1 of 21-Day Cycles 2, 3, 4, 5, 6, 9, 12, 15, 18, 19, 20, 21, 22, 23, 24, 27, 30, 33, 36, 39, 40, 42, 45, 48, 51, 54, 57, 60, 63, 66; Follow-up visit 1 (14 to 30 days after last study treatment) then continued follow-up every 3 months | The EORTC QLQ-C30 is a 30-item questionnaire used to assess the overall quality of life (QoL) in cancer participants. It consists of 15 domains: 1 Global Health Status (GHS)/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Reported here are the EORTC QLQ-C30 GHS/QoL scores only. GHS/QoL is derived from two items-"How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?"-each scored from 1 (very poor) to 7 (excellent). The average of these two items is linearly transformed to a 0-100 scale; higher scores indicate better overall quality of life, and a positive change from baseline reflects improvement. |
| Part 2: Change From Baseline in Global Health Status Score as Measured by the EORTC QLQ-C30 | Baseline, Day 1 of 21-Day Cycles 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36; Follow-up 1 (14 to 30 days after last study treatment) | The EORTC QLQ-C30 is a 30-item questionnaire used to assess the overall QoL in cancer participants. It consists of 15 domains: 1 Global Health Status (GHS)/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Reported here are the EORTC QLQ-C30 GHS/QoL scores only. GHS/QoL is derived from two items-"How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?"-each scored from 1 (very poor) to 7 (excellent). The average of these two items is linearly transformed to a 0-100 scale; higher scores indicate better overall quality of life, and a positive change from baseline reflects improvement. |
Countries
Austria, China, France, Georgia, Greece, Ireland, Italy, Lithuania, Malaysia, Poland, Romania, Russia, Slovakia, South Korea, Thailand, Turkey (Türkiye), Ukraine, United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.0 Years |
| Race/Ethnicity, Customized Asian | 12 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 763 Participants |
| Race/Ethnicity, Customized Not reported | 2 Participants |
| Race/Ethnicity, Customized White | 97 Participants |
| Sex: Female, Male Female | 125 Participants |
| Sex: Female, Male Male | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 84 / 108 | 80 / 109 | 80 / 103 | 7 / 31 | 232 / 312 | 129 / 153 |
| other Total, other adverse events | 102 / 108 | 97 / 109 | 94 / 103 | 19 / 31 | 288 / 312 | 136 / 153 |
| serious Total, serious adverse events | 38 / 108 | 39 / 109 | 23 / 103 | 7 / 31 | 95 / 312 | 38 / 153 |
Outcome results
None listed