Non-Small Cell Lung Cancer
Conditions
Sponsors
Regeneron Pharmaneuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Men and women =18 years of age (=20 years of age in Japan) 2.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. a.Patients who received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and developed recurrent or metastatic disease more than 6 months after completing therapy are eligible 3.Archival or newly obtained formalin-fixed tumor tissue from a metastatic/recurrent site, which has not previously been irradiated a.Tissue may be obtained from the primary site if it is still in place and the other metastatic sites are either not accessible (ie, brain), cannot be used (ie, bone), or the biopsy would put the patient at undue risk. b.If an archival biopsy is used, it must be less than 5 months old 4.Tumor cells expressing PD L1 in =50% of tumor cells by IHC performed by the central laboratory 5.At least 1 radiographically measureable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria (see Appendix 4). Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site. 6.ECOG performance status of =1 7.Anticipated life expectancy of at least 3 months 8.Adequate organ and bone marrow function as defined below: a.Hemoglobin =9.0 g/dL b.Absolute neutrophil count =1.5 × 109/L c.Platelet count =100,000/mm3 d.Glomerular filtration rate (GFR) >30 mL/min/1.73m2 e.Total bilirubin =1.5 × upper limit of normal (ULN) (if liver metastases =3 × ULN), with the exception of patients diagnosed with clinically confirmed Gilbert’s syndrome f.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 × ULN or =5 × ULN, if liver metastases g.Alkaline phosphatase =2.5 × ULN (or =5.0 × ULN, if liver or bone metastases) h.Not meeting criteria for Hy’s law (ALT >3 × ULN and bilirubin >2 × ULN) 9.Willing and able to comply with clinic visits and study-related procedures 10.Provide signed informed consent 11.Able to understand and complete study-related questionnaires Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 490 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 210
Exclusion criteria
Exclusion criteria: 1. Patients that have never smoked, defined as smoking =100 cigarettes in a lifetime 2. Active or untreated brain metastases or spinal cord compression. Patients are eligible if central nervous system (CNS) metastases are adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. Patients must be off (immunosuppressive doses of) corticosteroid therapy. 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. Patients with vitiligo, type I diabetes mellitus, and hypothyroidism (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement are permitted to be randomized. 7. Patients with a condition requiring corticosteroid therapy (>10 mg prednisone/day or equivalent) within 14 days of randomization. Physiologic replacement doses are allowed even if they are >10 mg of prednisone/day or equivalent, as long as they are not being administered for immunosuppressive intent. Inhaled or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder. 8. Another malignancy that is progressing or requires treatment, with the exception of nonmelanomatous skin cancer that has undergone potentially curative therapy, or in situ cervical carcinoma or any other tumor that has been treated, and the patient is deemed to be in complete remission for at least 2 years prior to randomization, and no additional therapy is required during the study period. 9. Uncontrolled infection with hepatitis B or hepatitis C or human immunodeficiency virus; or diagnosis of immunodeficiency 10. Exclusion criterion removed 11. Active infection requiring systemic therapy within 14 days prior to randomization 12. Prior therapy with anti-PD 1 or anti-PD L1. Prior exposure to other immunomodulatory or vaccine therapy such as anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies is permitted, but the last dose of such an antibody should have been at least 3 months prior to the first dose of study drug. 13. Treatment-related immune-mediated AEs from immune-modulatory agents (including but not limited to anti-PD1/PD-L1 mAbs, anti-CTLA4 mAbs, and phosphoinositol 3-kinase [PI 3-K]-d inhibitors) that have not resolved to baseline at least 3 months prior to initiation of treatment with study therapy. Patients are excluded from treatment with cemiplimab if they experienced immune-mediated AEs related to prior treatment with a blocker of the PD-1/PD-L1 pathway that were grade 3 or 4 in severity and/or required discontinuation of the agent, regardless of time of occurrence. 14. Receipt of an investigational drug or device within 30 days of screening or within 5 half lives of the investigational drug (whichever is longer) 15. Receipt of a live vaccine within 30 days of p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the study are: - To compare the OS of cemiplimab versus standard-of-care platinumbased chemotherapies in the first-line treatment of patients with advanced or metastatic 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 non-small cell lung cancer (NSCLC) whose tumors express programmed cell death ligand-1 (PD-L1) in =50% of tumor cells.;Secondary Objective: The key secondary objective of the study is to compare the ORR of cemiplimab versus platinum based chemotherapies.;Primary end point(s): The primary endpoints are OS and PFS as assessed by a blinded IRC using RECIST 1.1. Overall survival will be defined as the time from randomization to the date of death. A patient who has not died will be censored at the last known date of contact. Progression-free survival will be defined as the time from randomization to the date of the first documented tumor progression, as determined by the IRC (using RECIST 1.1) or death due to any cause. Patients will be censored according to rules listed below: 1.Patients who do not have a documented tumor progression or death will be censored on the date of their last evaluable tumor assessment. 2.Patients who do not have a documented tumor progression or death before initiation of new anti-tumor therapy will be censored on the date of their last evaluable tumor assessment prior to or on the date of new anti-tumor therapy. 3.Patients who withdraw consent before taking any study treatment, and as a consequence have no post-baseline tumor assessment, will be censored at the date of randomization. 4.Patients who do not have any evaluable tumor assessments after randomization and do not die will be censored on the date of randomization. ;Timepoint(s) of evaluation of this end point: Through 108 weeks of | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoint in the study will be ORR. Objective response rate will be defined as the number of patients with a best overall response (BOR) of confirmed CR or PR divided by the number of patients in the efficacy analysis set. Best overall response will be defined as the best overall response, as determined by the IRC per 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 comes first. ;Timepoint(s) of evaluation of this end point: Through 108 weeks of treatment | — |
Countries
Argentina, Australia, Belarus, Brazil, Bulgaria, Chile, China, Colombia, Czech Republic, Georgia, Greece, Hong Kong, Hungary, Italy, Malaysia, Mexico, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine
Contacts
Public ContactClinical Trial Information
Regeneron Pharmaceuticals, Inc.
Outcome results
None listed