A phase III comparative study of nivolumab (anti-PD-1; BMS-963558; ONO-4538) versus docetaxel in patients (pts) with previously treated advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC).

Abstract

TPS8121 Background: Lung cancer is the leading cause of cancer mortality globally. Non-squamous NSCLC represents up to 75% of NSCLC cases with most pts diagnosed with advanced disease, which progresses rapidly following failure of 1st-line platinum-based doublet (Pt-doublet) chemotherapy. Benefit from current therapies has reached a plateau with median overall survival (OS) for late stage NSCLC pts of 10-12 months. Standard 2nd-line therapy (single-agent chemotherapy; eg. docetaxel) results in OS of 8 months. Expression of programmed death-1 (PD-1), an immune checkpoint receptor that negatively regulates T-cell activation, is associated with poor prognosis in NSCLC. Nivolumab, a PD-1 receptor blocking antibody, prevents activation of PD-1 by its known ligands, PD-L1 and PD-L2, and demonstrated durable antitumor activity in NSCLC pts in a phase 1 study (Topalian ST, et al. N Engl J Med 2012). We present a phase III study comparing OS benefit of nivolumab vs docetaxel in pts with metastatic/recurrent non-squamous NSCLC. Methods: In this study, 574 pts will be randomized 1:1 to receive nivolumab 3 mg/kg IV q 2 weeks (wks) or docetaxel 75 mg/m2 q 3 wks until disease progression or unacceptable toxicity. Pts will include those having progressed during/after Pt-doublet ± bevacizumab (bev) for advanced disease as well as pts with EGFR-mutant or ALK-rearranged NSCLC who have progressed following treatment with a tyrosine kinase inhibitor (TKI) and a Pt-doublet ± bev. Prior maintenance therapy with erlotinib, pemetrexed and/or bev is allowed. Pts will be stratified by prior use of maintenance therapy and receipt of 1 vs 2 (Pt doublet and TKI) prior lines of therapy. Response will be assessed (modified RECIST 1.1) at 9 wks following treatment initiation and every 6 wks thereafter until disease progression. The primary objective is to compare the OS of nivolumab vs docetaxel treated pts. Secondary objectives include comparison of objective response rates, progression-free survival and disease related symptom progression, and evaluation of clinical benefit of nivolumab vs docetaxel in PD-L1+ vs PD-L1- tumor subgroups. Clinical trial information: NCT01673867.