Checkmate 73l: A Phase 3 Study Comparing Nivolumab Plus Concurrent Chemoradiotherapy Followed By Nivolumab +/- Ipilimumab Versus Concurrent Chemoradiotherapy Followed By Durvalumab For Previously Untreated, Locally Advanced Stage Iii Non-Small Cell Lung Cancer

Background: Historically, the standard-of-care for patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) was concurrent chemoradiotherapy (CCRT); however, outcomes are poor with 5-y survival rates of 15 – 30%. While CCRT primes anti-tumour immunity, it also upregulates PD-L1 expression, potentially blunting any immune response. Thus, concurrent immunotherapy + CCRT may improve outcomes. The safety and tolerability of nivolumab (NIVO), an anti-PD-1 antibody, given concomitantly with CCRT in pts with stage III NSCLC was demonstrated in the phase 2 NICOLAS study (NCT02434081). Furthermore, combining NIVO with ipilimumab (IPI), an anti-CTLA-4 antibody, resulted in a longer median overall survival (OS) versus chemotherapy in pts with advanced NSCLC who had a PD-L1 expression level of ≥ 1% in the phase 3 CheckMate 227 study (NCT02477826). In a prespecified exploratory analysis, NIVO + IPI showed an efficacy benefit versus NIVO. Previously, durvalumab (DURV), an anti-PD-L1 antibody, demonstrated significant improvements versus placebo in progression-free survival (PFS) and OS with manageable safety in pts without disease progression after CCRT in the phase 3 PACIFIC study (NCT02125461). Therefore, we will evaluate the efficacy of NIVO + CCRT followed by NIVO ± IPI versus CCRT followed by DURV for untreated, locally advanced stage III NSCLC in the phase 3 randomized CheckMate 73 L study (NCT04026412).