CheckMate 73L: A Phase 3 Study Comparing Nivolumab Plus Concurrent Chemoradiotherapy Followed by Nivolumab With or Without Ipilimumab Versus Concurrent Chemoradiotherapy Followed by Durvalumab for Previously Untreated, Locally Advanced Stage III Non-Small-Cell Lung Cancer

Abstract

Introduction: The 5 year survival rate for patients with locally advanced non-small-cell lung cancer (NSCLC) not amenable for definitive resection with historical standard-of-care concurrent chemoradiotherapy (cCRT) ranges from 15% to 32%. cCRT primes anti-tumor immunity and also upregulates programmed death ligand-1 (PD-L1), providing a rationale for combining an immune checkpoint inhibitor with cCRT to improve outcomes. In the PACIFIC trial, consolidation therapy with the PD-L1 inhibitor durvalumab improved progression-free survival (PFS) and overall survival (OS) vs. placebo in patients with stage III NSCLC who did not have disease progression after cCRT. CheckMate73L (NCT04026412), a randomized phase 3 study, evaluates the efficacy of nivolumab plus cCRT followed by nivolumab with or without ipilimumab vs. cCRT followed by durvalumab for untreated, stage III NSCLC.

Patients and methods: Patients with untreated, stage III NSCLC will be randomized 1:1:1 to nivolumab plus cCRT followed by nivolumab in combination with ipilimumab (Arm A) or nivolumab alone (Arm B); or cCRT followed by durvalumab (Arm C). Primary endpoints are PFS and OS (Arm A vs. Arm C). Secondary endpoints include additional analyses of PFS and OS (Arm A vs. Arm B; Arm B vs. Arm C), as well as objective response rate, complete response rate, time to response, duration of response, time to death or distant metastases, and safety and tolerability. Recruitment began on August 20, 2019, and the estimated primary completion date is October 17, 2022.

Keywords: Chemoradiation; Cytotoxic T-lymphocyte antigen-4; Immune checkpoint inhibitor; PD-1/PD-L1; Progression-free survival.