CA184-104: Randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab (Ipi) with paclitaxel/carboplatin (PC) versus placebo with PC in patients (pts) with stage IV/recurrent non-small cell lung cancer (NSCLC) of squamous histology.

TPS7611 Background: Years of research in advanced NSCLC have not improved outcomes for the squamous subtype beyond those of standard platinum doublets. Evidence of responses to immune therapies in NSCLC of squamous cell histology supports investigation in this subtype. Ipi, a fully human monoclonal antibody which blocks CTLA-4, augments antitumor immune responses. Ipi improved overall survival (OS) in advanced melanoma, with side effects managed using product-specific treatment guidelines; immune-related response criteria (irRC) were derived from WHO criteria to better capture response patterns observed with Ipi. A randomized Phase 2 study of Ipi/PC in Stage IV NSCLC pts showed significant improvement in progression-free survival (PFS), as measured by mWHO or irRC, with a trend toward improved OS, over chemotherapy alone in pts receiving phased Ipi/PC (Ipi started after 2 cycles of PC). Phased Ipi/PC appeared to show efficacy in tumors of squamous histology. Addition of Ipi did not exacerbate PC toxicity, and immune-related adverse events were managed using protocol-specific guidelines. A Phase 3 trial (ClinicalTrials.gov identifier NCT01285609) is examining whether phased Ipi/PC will prolong OS in chemotherapy-naïve pts with squamous NSCLC. Methods: Stage IV/recurrent squamous NSCLC with ECOG 0-1 will be included; pts with CNS metastases or history of autoimmune disease will be excluded. Pts are randomized to receive 2 cycles of PC (175 mg/m 2 and AUC=6, respectively; IV), followed by 4 cycles of study drug (Ipi in Arm A, placebo in Arm B; IV) with 4 additional cycles of PC (total 6 cycles). Pts without progressive disease (PD) after induction receive maintenance therapy with blinded study drug Q12W until PD per mWHO. The study will randomize 920 pts 1:1 between arms. The primary endpoint of this study is OS; secondary endpoints include OS among pts who receive blinded therapy, PFS and best overall response rate.