Carcinoma，Non-Small-Cell Lung, Lung Carcinomas, Non-Small-Cell, Nonsmall Cell Lung Cancer, Non-small-cell Lung Carcinoma
Conditions
Keywords
Previous Smoker, Current Smoker, Stage IIIB, Stage IIIC, Stage IV, PD-L1
Brief summary
The primary objectives of the study are: * To compare the overall survival (OS) of cemiplimab versus standard-of-care platinum-based chemotherapies in the first-line treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 in ≥50% of tumor cells * To compare the progression-free survival (PFS) of cemiplimab versus standard-of-care platinum-based chemotherapies in the first-line treatment of patients with advanced or metastatic NSCLC whose tumors express PD-L1 in ≥50% of tumor cells The key secondary objective of the study is to compare the objective response rate (ORR) of cemiplimab versus platinum-based chemotherapies
Detailed description
There is option to join genomics sub-study.
Interventions
DRUGcemiplimab
Patients will be administered cemiplimab as per protocol.
DRUGPemetrexed
Patients will be administered pemetrexed chemotherapy as per protocol with either cisplatin or carboplatin
DRUGPaclitaxel
Patients will be administered paclitaxel chemotherapy as per protocol with either cisplatin or carboplatin
DRUGGemcitabine
Patients will be administered gemcitabine chemotherapy as per protocol with either cisplatin or carboplatin
DRUGCisplatin
Administered with either Pemetrexed, Paclitaxel or gemcitabine.
DRUGCarboplatin
Administered with either Pemetrexed, Paclitaxel or gemcitabine.
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: A patient must meet the following criteria to be eligible for inclusion in the study: 1. Patients with histologically or cytologically documented squamous or non squamous NSCLC with stage IIIB or stage IIIC disease who are not candidates for treatment with definitive concurrent chemoradiation or patients with stage IV disease who received no prior systemic treatment for recurrent or metastatic NSCLC 2. Archival or newly obtained formalin-fixed tumor tissue from a metastatic/recurrent site, which has not previously been irradiated 3. Tumor cells expressing PD L1 above a specific percentage of tumor cells by IHC performed by the central laboratory 4. At least 1 radiographically measureable lesion per RECIST 1.1 5. ECOG performance status of ≤1 6. Anticipated life expectancy of at least 3 months 7. Adequate organ and bone marrow function Key
Exclusion criteria
A patient who meets any of the following criteria will be excluded from the study: 1. Patients that 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 EGFR gene mutations, ALK gene translocations, or ROS1 fusions 4. Encephalitis, meningitis, or uncontrolled seizures in the year prior to randomization 5. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to randomization 6. Patients with active, known, or suspected autoimmune disease that has required systemic therapy in the past 2 years 7. Patients with a condition requiring corticosteroid therapy (\>10 mg prednisone/day or equivalent) within 14 days of randomization 8. Another malignancy that is progressing or requires treatment 9. Uncontrolled infection with hepatitis B or hepatitis C or human immunodeficiency virus (HIV) or diagnosis of immunodeficiency 10. Active infection requiring systemic therapy within 14 days prior to randomization 11. Prior therapy with anti-PD 1 or anti-PD L1 12. Treatment-related immune-mediated AEs from immune-modulatory agents 13. Receipt of an investigational drug or device within 30 days 14. Receipt of a live vaccine within 30 days of planned start of study medication 15. Major surgery or significant traumatic injury within 4 weeks prior to first dose 16. Documented allergic or acute hypersensitivity reaction attributed to antibody treatments 17. Known psychiatric or substance abuse disorder that would interfere with participation with the requirements of the study, including current use of any illicit drugs 18. Pregnant or breastfeeding women 19. Women of childbearing potential or men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 94 months | OS was defined as the time from randomization to the date of death due to any cause. |
| Progression-free Survival (PFS) Per Blinded IRC | Up to 94 months | PFS as assessed by blinded 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per IRC | Up to 73.5 months | ORR was defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as assessed by IRC per RECIST 1.1. |
| Best Overall Response (BOR) Per IRC | Up to 73.5 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. |
| Duration of Response (DoR) Per IRC | Up to 73.5 months | DoR was defined as the time from date of first documented response of CR or PR to the date of first documented PD (per RECIST 1.1) or death due to any cause, whichever occurred earlier. |
| Change From Baseline in Global Health Status/Quality of Life (QoL) Scores as Assessed by the European Organisation 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, 21, 24, 27, 30, 33, 36, 39 | 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 score ranging from 0 to 100; higher scores indicate better overall quality of life, and a positive change from baseline reflects improvement. |
| Change From Baseline in Coughing Scores as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) | Baseline, Day 1 of 21-Day Cycles 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 | EORTC QLQ-LC13 is a 13-item questionnaire used in clinical research to assess health-related quality of life in lung cancer patients. The QLQ-LC13 includes questions assessing lung cancer-associated symptoms (coughing, haemoptysis, dyspnoea and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy and alopecia). Reported here are the EORTC lung cancer coughing scores only. Scores were calculated and transformed to a range from 0 to 100, with a higher score representing a higher level of symptoms/problems and a negative change from baseline value indicating reduction (i.e. improvement) in symptoms. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to 94 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. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Number of Participants With Serious TEAEs | Up to 94 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. |
| Number of Deaths During the On-Treatment Period | Up to approximately 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. |
| Number of Participants With Laboratory Abnormalities | Up to approximately 28 months | Reported here is the number of participants with at least one laboratory abnormality of any grade in measurements for hematology, electrolytes, liver function, chemistry, and coagulation. |
| Trough Concentration (Ctrough) of Cemiplimab in Serum | Up to 73.5 months | — |
| Maximum Plasma Concentration (Cmax) of Cemiplimab in Serum | Up to 73.5 months | — |
| Number of Participants With Anti-Cemiplimab Antibodies (ADA) | Up to 73.5 months | The ADA status of each participant was classified as one of the following: * Pre-existing - If the baseline sample is positive and all post baseline ADA titers are reported as less than 9-fold the baseline titer value * Negative - If all samples are found to be negative in the ADA assay * Treatment-emergent response |
| Number of Participants With Neutralizing Antibodies (NAb) | Up to 73.5 months | The NAb status of each participant was categorized as follows: * Negative - Samples that tested negative in the ADA assay, or samples positive in the ADA assay but tested negative in the NAb assay * Positive |
Countries
Australia, Belarus, Brazil, Bulgaria, Chile, China, Colombia, Czechia, Georgia, Greece, Hungary, Jordan, Lebanon, Malaysia, Mexico, Philippines, Poland, Romania, Russia, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 8.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 328 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 6 Participants |
| Race/Ethnicity, Customized Asian | 38 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized White | 615 Participants |
| Sex: Female, Male Female | 105 Participants |
| Sex: Female, Male Male | 313 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 178 / 356 | 60 / 85 | 116 / 343 | 141 / 191 |
| other Total, other adverse events | 287 / 356 | 70 / 85 | 319 / 343 | 141 / 191 |
| serious Total, serious adverse events | 131 / 356 | 23 / 85 | 103 / 343 | 57 / 191 |
Outcome results
None listed