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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
P1.01-082 - A Phase III Study of MEDI4736 (M) an Anti-PD-L1 Antibody ± Tremelimumab (T), vs Standard of Care (SoC), in Patients with Advanced NSCLC (ARCTIC) (ID 1237)
09:30 - 17:00 | Author(s): M. Shtivelband
M is a human IgG1 mAb that blocks programmed cell death ligand-1 (PD-L1) binding to programmed cell death-1 and CD-80 with high affinity and selectivity, and T is a selective human IgG2 mAb inhibitor of cytotoxic T-lymphocyte antigen-4 (CTLA-4). Both PD-L1 and CTLA-4 are regulators, or checkpoints, of T-cell activation. PD-L1 expression may be associated with greater clinical benefit of anti-PD-1/PD-L1 agents. Thus, the subset of patients with PD-L1-negative tumors represent a cohort with limited therapeutic options, and may benefit from the combination of M+T. Preclinical data, including mouse models of transplantable solid tumors, suggest that targeting both pathways may have synergistic antitumor activity. Emerging pharmacokinetics, pharmacodynamics, safety and efficacy data from a phase Ib study of M+T in advanced NSCLC (NCT02000947) has determined the appropriate dose for this combination.
This randomized, open label, multi-center, phase III study (NCT02352948) is designed to evaluate the efficacy and safety of M (10mg/kg once every 2 weeks [Q2W] for up to 12 months) vs SoC (gemcitabine 1000 mg/m iv Days 1, 8, and 15, vinorelbine 30 mg/m iv on Days 1, 8, 15 and 22 or erlotinib 150 mg once daily, on a 4-weekly schedule until PD at the investigator’s discretion) in NSCLC patients with PD-L1-positive tumors (based on archival tumor sample or recent biopsy) (Sub-study A), and the combination of M+T (M 20mg/kg + T 1mg/kg Q4W for 12 weeks then M alone 10mg/kg Q2W for 34 weeks) vs M or T (10mg/kg Q4W for 24 weeks then Q12W for 24 weeks) vs SoC in NSCLC patients with PD-L1-negative tumors (Sub-study B). PD-L1-positive is defined as ≥25% of tumor cells with membrane staining based on central assessment. Approximately 300 patients will be randomized 1:1 in Sub-study A and approximately 600 patients in a 3:2:2:1 ratio (M+T or SoC or M or T) in Sub-study B. Retreatment with immune-therapy is allowed within the setting of PD. For both sub-studies, an interim analysis for OS (and also PFS for Sub-study B) will be performed. Eligible patients include patients (PS of 0-1) with locally advanced or metastatic NSCLC, who have received at least 2 prior treatment regimens including 1 platinum-based chemotherapy. Patients with brain metastases or spinal cord compression are excluded unless asymptomatic, treated and stable off steroids. Patients with known EGFR activating mutations or ALK rearrangements are not eligible, nor patients previously exposed to any anti-PD-1 or anti-PD-L1 antibody. The primary objective is to assess PFS (per RECIST 1.1 as assessed by the Blinded Independent Central Review) and OS of M (PD-L1-positive) and M+T (PD-L1-negative), compared with SoC, in sub-study A and B, respectively. Secondary objectives include proportion of patients alive at 12 months, objective response rate, duration of response, PFS at 6 and 12 months, safety, tolerability, pharmacokinetics, immunogenicity and health-related QoL. Tumor assessments are performed every 8 weeks (first 48 weeks) then every 12 weeks. A confirmatory scan is required following the initial demonstration of PD. Recruitment in the study is ongoing since January 2015.
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