A phase III comparative study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) versus docetaxel in patients with previously treated advanced or metastatic squamous cell non-small cell lung cancer (NSCLC).

Abstract

TPS8122 Background: NSCLC is the leading cause of cancer death worldwide, exceeding breast, colon and prostate cancer combined. Most patients (pts) are diagnosed with advanced/recurrent disease. NSCLC therapies have incrementally improved overall survival (OS), but benefit has reached a plateau (median OS for late stage pts is just 1 yr). Squamous cell carcinoma (SCC) represents one quarter of NSCLC cases and has limited treatment options. Pemetrexed and bevacizumab are not approved in SCC, and molecularly targeted therapies have limited application. Single-agent chemotherapy is standard of care following progression with platinum-based doublet chemotherapy (Pt-doublet), resulting in median OS of approximately 7 months. Immune checkpoint blockade in NSCLC may promote tumor regression by reversing tumor-induced immunosuppression and restoring the antitumor immune response. Programmed death-1 (PD-1), an immune checkpoint receptor that negatively regulates T-cell activation, is upregulated in tumor infiltrating lymphocytes; expression of its ligand PD-L1 has been associated with poor prognosis in NSCLC. Nivolumab, a PD-1 receptor blocking antibody, showed encouraging antitumor activity in SCC pts in a phase 1 study, with objective responses (ORs) in 4 pts (27%) and stable disease ≥24 weeks in 1 pt (7%) (3 mg/kg; n=15) (Gettinger S et al; ESMO 2012 [Abstr 1237PD]). We describe an ongoing open-label phase 3 study to compare the clinical benefit of nivolumab vs docetaxel in advanced/metastatic SCC pts following failure of Pt-doublet. Methods: A total of 264 pts will be randomized 1:1 to nivolumab monotherapy 3 mg/kg IV every 2 weeks or docetaxel 75 mg/m2 every 3 weeks until disease progression or unacceptable toxicity. Pts will be stratified by prior paclitaxel use and geographic region. Tumor response will be assessed using modified RECIST 1.1. The co-primary objectives are OR rate and OS. Secondary objectives include progression free survival, clinical benefit in PD ligand 1 (PD-L1+) and PD-L1– subgroups (archived tissue required for entry), durability of and time to OR, and pt proportion with symptom improvement. Clinical trial information: NCT01642004.