CheckMate 73 L: 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).

Trial Design: In all, 888 pts aged ≥ 18 y with previously untreated stage III NSCLC and an ECOG PS ≤ 1 will be stratified by age, PD-L1 expression, and disease stage, then randomized (1 : 1 : 1) to receive NIVO (360 mg Q3W) + CCRT followed by NIVO (360 mg Q3W) + IPI (1 mg/kg Q6W; Arm A) or NIVO alone (480 mg Q4W; Arm B) for ≤ 1 y, or CCRT followed by DURV (10 mg/kg Q2W; Arm C) for ≤ 1 y. Pts with progressive disease during CCRT will discontinue treatment and enter follow-up. Primary endpoints are PFS by RECIST 1.1, assessed by BICR (Arm A vs. C) and OS (Arm A vs. C). Secondary endpoints are PFS (Arm B vs. A or C), OS (Arm B vs. A or C), objective response rate, time to response, duration of response, time to distant metastases, and safety. Start date: Aug 2019.

^* Previously presented at ESMO Congress 2020, #1255 TiP, De Ruysscher D et al. – Reused with permission.

Publication History

Article published online:
30 April 2021