This is a phase 2 multicenter, open label, randomized study of AMG 951 (rhApo2L/TRAIL) in subjects with previously untreated stage IIIb/IV NSCLC treated with chemotherapy with or without bevacizumab. Subjects will be assigned to a set of treatment groups depending on their eligibility to receive bevacizumab. Subjects with squamous NSCLC and/or CNS metastases will not be eligible to receive bevacizumab and will be assigned to either cohort A or B (provided all other eligibility criteria are met). Subjects who are eligible to receive bevacizumab will be assigned to cohort C, D or E. Cohorts are defined as follows: Subjects with squamous NSCLC or CNS mets: Cohort A: Chemotherapy alone Cohort B: Chemotherapy plus 8 mg/kg AMG 951 for 5 days Subjects without squamous NSCLC and without CNS mets: Cohort C: Chemotherapy and bevacizumab Cohort D: Chemotherapy, bevacizumab plus 8 mg/kg AMG 951 for 5 days Cohort E: Chemotherapy, bevacizumab plus up to 20 mg/kg AMG 951 for 2 days Approximately forty subjects will be recruited to each cohort.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
213
AMG 951 is recombinant human Apo2Ligand/Tumor necrosis factor related apoptosis inducing ligand (rhApo2L/TRAIL) that triggers apoptosis through activation of death receptor 4 (DR4) and death receptor 5 (DR5).
Bevacizumab is a recombinant humanized version of a murine antibody to vascular endothelial growth factor (VEGF).
Standard platinum based chemotherapy
Standard taxane chemotherapy
Objective response rate (CR and PR) by modified RECIST
Time frame: Until disease progression, drug intolerability or withdrawal of consent
Progression free survival
Time frame: Until disease progression, drug intolerability or withdrawal of consent
Time to response
Time frame: Until disease progression, drug intolerability or withdrawal of consent
Duration of response
Time frame: Until disease progression, drug intolerability or withdrawal of consent
Time to progression
Time frame: Until disease progression, drug intolerability or withdrawal of consent
Overall response rate (complete, partial or stable response)
Time frame: Until disease progression, drug intolerability or withdrawal of consent
Overall Survival
Time frame: Until disease progression, drug intolerability or withdrawal of consent
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