non-small cell lung cancer
Conditions
Interventions
- avelumab at a dose of 10 mg/kg as a 1-hour intravenous (IV) infusion once
every 2 weeks, or
- docetaxel at a starting dose of 75 mg/m2 (per label) by IV infusion once
every 3 weeks.
avelumab
docetaxel
non-small cell lung cancer
Sponsors
Merck
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent before any trial related procedure is undertaken that is not part of the standard patient management 2. Male or female subjects aged * 18 years 3. Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or 7 unstained tumor slides suitable for PD-L1 expression assessment 4. Tumor determined to be evaluable for PD-L1 expression per the evaluation of a central laboratory 5. Subjects with histologically confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression 6. 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 7. 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 8. ECOG PS of 0 to 1 at trial entry 9. Estimated life expectancy of more than 12 weeks 10. 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) 11. 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 12. Adequate renal function defined by an estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) 13. Effective contraception for both male and female subjects if the risk of conception exists (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use effective contraception, defined as 2 barrier methods, or 1 barrier method with a spermicide, an intrauterine device, or use of oral female contraceptive. Effective contraception must be used 30 days prior to first trial drug administration, for the duration of trial participation, and at least for 60 days after stopping trial participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the
Exclusion criteria
Exclusion criteria: 1. In the United States only, subjects with a squamous cell histology will be excluded 2. 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 3. 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 4. 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 5. Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy], immune therapy, or cytokine therapy except for erythropoietin) 6. 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 7. Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of patients with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to < 10 mg prednisone daily). Note: Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before first dose of trial treatment 8. 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 (sequelae that are a consequence of the treatment of the brain metastases are acceptable) 9. Previous malignant disease (other than NSCLC) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder, cervical, colorectal, breast) 10. Prior organ transplantation, including allogeneic stem cell transplantation 11. Significant acute or chronic infections including, among others: * Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome * Any positive test for HBV or HCV indicating acute or chronic infection (test to be conducted at Screening) 12. 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 thro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint for the trial is OS time, defined as the time (in months) from randomization to the date of death. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints include - PFS time according to RECIST 1.1 and as adjudicated by the IERC, - BOR according to RECIST 1.1 and as adjudicated by the IERC, - changes in subject-reported outcomes / quality of life as assessed by the EQ-5D and the EORTC QLQ-C30 and module QLQ LC13 questionnaire, and - the safety profile of the trial drugs as measured by the incidence of AEs, serious AEs (SAEs), clinical laboratory assessments, vital signs, physical examination, ECG parameters, and ECOG PS. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Chile, Colombia, Croatia, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Korea (the Republic of), Mexico, Netherlands, Peru, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Switzerland, Taiwan (Province of China), Turkey, United Kingdom, United States of America
Outcome results
None listed