Non-Small Cell Lung Cancer MedDRA version: 20.1 Level: LLT Classification code 10025048 Term: Lung cancer non-small cell recurrent System Organ Class: 100000004864
Conditions
Interventions
Product Name: cemiplimab
Product Code: REGN2810
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: cemiplimab
Current Spons
Sponsors
Regeneron Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women =18 years of age 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 chemo-radiation or patients with stage IV disease. Patients must have PD after receiving one prior line of chemotherapy treatment for advanced NSCLC. 3. Availability of an archival or on-study obtained formalin-fixed, paraffin-embedded tumor tissue biopsy sample. Guidance on biopsy sites: a. Archival or fresh biopsies are acceptable; b. If an archival biopsy is used, it has to be less than 5 months old; c. The biopsy should be from a metastatic or recurrent site which has not previously been irradiated. Exception: the primary tumor is still in place and the other metastatic sites are either not accessible (brain) or cannot be used (bone) or the biopsy would put the patient at risk 4. Biopsy evaluable for expression of PD-L1 as determined by the PD-L1 IHC 22C3 pharmDx assay performed by the central laboratory 5. At least 1 radiographically measureable lesion by computed tomography (CT) 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. ECOG performance status of =1 7. 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 =75,000/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. ALT =65 years) yes F.1.3.1 Number of subjects for this age range 63
Exclusion criteria
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. 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 (see exclusion criteria 7) for details on timing of discontinuation of steroids) 3. Patients with tumors tested positive for EGFR gene mutations, ALK gene translocations, or ROS1 fusions. All patients will have their tumor evaluated for EGFR mutations, ALK rearrangement, and ROS1 fusions by a central laboratory. 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. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved =6 months prior to randomization. 6. Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest a risk of immune-related treatment emergent adverse events (irTEAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment 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. Previous treatment with idelalisib (ZYDELIG®) at any time 9. Prior treatment with an anti-CTLA-4 antibody or anti-PD-1/PD-L1 for lung cancer 10. Another malignancy that is progressing or requires treatment, with the exception of nonmelanomatous skin cancer that has undergone potentially curative therapy, in situ cervical carcinoma, or any other localized 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 11. Known active hepatitis B (known positive result) or hepatitis C (known positive result) and known quantitative HCV RNA results greater than the lower limits of detection of the assay). Uncontrolled infection with human immunodeficiency virus, (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency. 12. Active infection requiring systemic therapy within 14 days prior to randomization 13. Treatment-related immune-mediated AEs from immune-modulatory agents (including but not limited to anti-PD1/PD-L1 monoclonal antibodies, anti-CTLA4 monoclonal antibodie
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The primary endpoint of ORR will be analyzed when all enrolled patients have an opportunity to complete 7 months of study treatment and have had at least two on-treatment tumor assessments. ;Main Objective: 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.; Secondary Objective: -To compare the ORR of HDREGN2810 and SDREGN2810/ipi to the ORR of SDREGN2810 in the second-line treatment of patients with advanced squamous or non-squamous NSCLC in all patients. -To compare the OS of HDREGN2810, and SDREGN2810/ipi combination therapy compared to the OS of SDREGN2810 in the second-line treatment of patients with advanced squamous or non-squamous NSCLC in patients with PD-L1 in <50% of tumor cells and in all patients. -To compare the PFS of HDREGN2810 and SDREGN2810/ipi combination therapy to the PFS of SDREGN2810 in the second-line treatment of patients with advanced squamous or non-squamous NSCLC in patients with PD-L1 in <50% of tumor cells and in all patients. -To evaluate the safety and tolerability of HDREGN2810 and SDREGN2810/ipi compared to those of SDREGN2810 therapy ; Primary end point(s): The primary endpoint is objective response rate (ORR) defined as the proportion of patients achieving CR or PR as assessed by a blinded IRC based on RECIST 1.1 a | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Objective response rate in all patients -Overall survival in patients whose tumors express PD-L1 in <50% of tumor cells and in all patients. Overall survival is defined as the time from randomization to the date of death. A patient who is lost to follow-up will be censored at the last date that the patient was known to be alive. -PFS in patients whose tumors express PD-L1 in <50% of tumor cells and in all patients. Progression-free survival is 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. Patients will be censored according to the rules listed below: o Patients without a documented tumor progression or death will be censored on the date of their last evaluable tumor assessment. o Patients without any evaluable tumor assessments after randomization and did not die will be censored on the date of randomization. -The incidences of TEAEs, serious adverse events (SAEs), deaths, and laboratory abnormalities. ;Timepoint(s) of evaluation of this end point: The secondary endpoint of OS will be analyzed 12 months after the analysis of ORR. The secondary endpoint of PFS will be analyzed at the same time as analysis of ORR. | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Korea, Republic of, Netherlands, Poland, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Regeneron Pharmaceuticals, Inc.
Outcome results
None listed