Non-Small Cell Lung Cancer MedDRA version: 18.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Avelumab
Product Code: MSB0010718C
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Avelumab
Current Sponsor code: MSB0010718C
Other descriptive name: Anti
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria: - Signed written informed consent before any trial related procedure - Male or female subjects aged = 18 years - Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or 7 unstained tumor slides suitable for PD-L1 expression assessment - Tumor determined to be evaluable for PD-L1 expression per the evaluation of a central laboratory - Subjects with histologically confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression - Subjects must have progressed after an acceptable therapy defined as follows: a. Subjects must have progressed during or after a minimum of 2 cycles of 1 course of a platinum based combination therapy administered for the treatment of a metastatic disease. A history of continuation (use of a non platinum agent from initial combination) or switch (use of a different agent) maintenance therapy is permitted provided there was no progression after the initial combination. A switch of agents during treatment for the management of toxicities is also permitted provided there was no progression after the initial combination OR b. Subjects must have progressed within 6 months of completion of a platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for locally advanced disease - Subjects with non-squamous cell NSCLC of unknown EGFR mutation status will require testing (local laboratory, or central laboratory if local testing is not available). For subjects with a tumor that harbors an activating EGFR mutation, acceptable prior therapy is also defined as a treatment with an EGFR-targeting tyrosine kinase inhibitor (TKI) given before or after treatment with a platinum-based combination chemotherapy as defined above. Subjects with a tumor that harbors an activating EGFR mutation must have failed both the platinum-based doublet and the EGFR-targeting TKI. Treatment with more than 1 EGFR targeting TKI is acceptable - ECOG PS of 0 to 1 at trial entry - Estimated life expectancy of more than 12 weeks - Adequate hematological function defined by WBC count = 2.5 × 109/L with absolute neutrophil count (ANC) = 1.5 × 109/L, lymphocyte count = 0.5 × 109/L, platelet count = 100 × 109/L, and hemoglobin = 9 g/dL (may have been transfused) - Adequate hepatic function defined by a total bilirubin level = 1.0 × the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels = 2.5 × ULN for all subjects - Adequate renal function defined by an estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) Other protocol defined criteria could apply 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 455 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 195
Exclusion criteria
Exclusion criteria: Exclusion criteria - In the United States only, subjects with a squamous cell histology will be excluded - Systemic anticancer therapy administered after disease progression during or following a platinum based combination, with the following exception: Subjects whose disease harbors an activating EGFR mutation who received an EGFR inhibitor AFTER a minimum of 2 cycles of first-line platinum-based therapy. Subjects who tested undetermined or wild-type for EGFR but were previously treated with a TKI are not eligible unless retested and confirmed to be activating EGFR mutation positive - Subjects with non-squamous cell NSCLC whose disease harbors an anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial. Subjects of unknown ALK status will require testing for ALK rearrangement (local laboratory, or central laboratory if local testing is not available) and must be determined to be ALK wild-type to be eligible for this trial - Prior therapy with any antibody/drug targeting T cell coregulatory proteins (immune checkpoints) such as PD-1, PD L1, or cytotoxic T lymphocyte antigen-4 (CTLA-4). Prior therapy with a cancer vaccine is acceptable - Concurrent anticancer treatment - Major surgery for any reason, except diagnostic biopsy, within 4 weeks of randomization and/or if the subject has not fully recovered from the surgery within 4 weeks of randomization - Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment. - All subjects with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, and b. No ongoing neurological symptoms that are related to the brain localization of the disease - Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible b. Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses = 10 mg or 10 mg equivalent prednisone per day c. Administration of steroids through a route known to result in a minimal systemic exposure are acceptable - Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be = 10 mg per day of equivalent prednisone Other protocol defined criteria could apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate superiority with regard to overall survival (OS) of avelumab versus docetaxel in subjects with programmed death ligand 1 (PD-L1) positive (+; as determined by a companion diagnostic test under development), non-small cell lung cancer (NSCLC) after failure of a platinum-based doublet;Secondary Objective: Secondary objectives are as follows: • To demonstrate superiority with regard to OS of avelumab versus docetaxel in the intention-to-treat (ITT) population • To demonstrate superiority with regard to the objective response rate (ORR) of avelumab versus docetaxel in PD-L1+ subjects • To demonstrate superiority with regard to progression free survival (PFS) of avelumab versus docetaxel in PD-L1+ subjects • To demonstrate superiority with regard to the ORR of avelumab versus docetaxel in the ITT population • To demonstrate superiority with regard to PFS of avelumab versus docetaxel in the ITT population • To compare the subject-reported outcomes / quality of life when treated with avelumab versus docetaxel using the EuroQOL 5-dimensions questionnaire (EQ 5D) and the European Organization for Research and Treatment of Cancer (EORTC) QLQ C30 and module QLQ-LC13 in the ITT population • To determine the safety and tolerability of avelumab ;Primary end point(s): Overall survival time;Timepoint(s) of evaluation of this end point: Time from 1st randomization up to 21 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: –Progression-Free Survival (PFS) Time –Best Overall Response (BOR) –Quality of Life EuroQuol-5D Health Outcome Questionnaire –Quality of Life Assessment European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status –Quality Of Life Assessment EORTC Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13) – Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 ;Timepoint(s) of evaluation of this end point: Time from 1st randomization up to 21 months | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Chile, Colombia, Croatia, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Latvia, Mexico, Netherlands, Peru, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactCommunication Centre Merck KGaA
Merck KGaA
Outcome results
None listed