CheckMate 451: A randomized, double-blind, phase III trial of nivolumab (nivo), nivo plus ipilimumab (ipi), or placebo as maintenance therapy in patients (pts) with extensive-stage disease small cell lung cancer (ED-SCLC) after first-line platinum-based doublet chemotherapy (PT-DC).

Abstract

TPS8579 Background: Most SCLC pts present with ED-SCLC. Initial response rates are high, but disease often rapidly recurs or progresses. Outcomes with second-line treatment are poor. No maintenance therapy has been approved for pts who respond to first-line PT-DC. Nivo, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor, is approved for previously treated metastatic NSCLC in the US and for previously treated squamous NSCLC in the EU based on 2 phase III trials demonstrating superior survival over docetaxel. Nivo monotherapy and nivo + ipi, a fully human IgG1 cytotoxic T lymphocyte antigen-4 immune checkpoint inhibitor, are being evaluated in previously treated pts with advanced or metastatic SCLC in a phase I/II trial (CheckMate 032, SCLC cohort). Nivo (vs chemotherapy) is also being evaluated in relapsed SCLC in a phase III trial (CheckMate 331). From CheckMate 032, preliminary data of nivo and nivo + ipi has shown antitumor activity with durable tumor responses and manageable safety profiles in pts with SCLC in the second-line setting or later. Responses were observed regardless of programmed death ligand 1 expression or platinum sensitivity/resistance. Based on these promising data, a phase III trial (CheckMate 451) was designed to evaluate nivo monotherapy, nivo + ipi followed by nivo monotherapy, and placebo as maintenance therapy for ED-SCLC after first-line PT-DC. Methods: Adult pts with ED-SCLC who achieve stable disease or better after first-line PT-DC and have ECOG performance status 0–1 are eligible. Pts with active central nervous system metastases, autoimmune disease, or toxicities attributed to prior anticancer therapy not resolved to grade ≤ 1 are ineligible. Primary endpoints are overall survival and progression-free survival. Approximately 810 pts will be enrolled and randomized to nivo monotherapy, nivo + ipi followed by nivo monotherapy, or placebo. Clinical trial information: NCT02538666.