Overall Survival with Neoadjuvant Nivolumab (NIVO) + Chemotherapy (chemo) in Patients with Resectable NSCLC in CheckMate 816.

LBA8000 Background: NIVO + chemo is an established standard of care neoadjuvant treatment (tx) for eligible patients (pts) with resectable NSCLC and has shown statistically significant and clinically meaningful improvements in EFS and pCR in the phase 3 CheckMate 816 study. Here, we report the planned final analysis of OS from CheckMate 816 at 5-y follow-up (f/u). Methods: Adults with stage IB (≥ 4 cm)–IIIA (per AJCC v7) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR / ALK alterations were randomized 1:1 to receive neoadjuvant NIVO + chemo Q3W or chemo alone Q3W for 3 cycles, followed by surgery. Primary endpoints were EFS and pCR (both by blinded independent review). OS was a key prespecified, statistically powered secondary endpoint that was tested hierarchically. Exploratory analyses included OS by ctDNA clearance and pCR status. Results: At a median f/u of 68 mo (range, 60–85; database lock, 23 Jan 2025), neoadjuvant NIVO + chemo demonstrated a statistically significant OS benefit vs chemo alone (median [95% CI], not reached [NR] vs 73.7 mo [47.3–NR]; HR [95% CI], 0.72 [0.523–0.998]; P = 0.0479); 5-y OS rates were 65% vs 55%. OS favored NIVO + chemo in the subgroups defined by tumor PD-L1 expression, baseline disease stage, and histology (Table). In an exploratory analysis in pts with ctDNA+ at baseline (NIVO + chemo, n = 43; chemo, n = 43), pts with presurgical ctDNA clearance (56% vs 35%) had continued OS improvement vs those without across both tx arms (HR [95% CI]: NIVO + chemo, 0.38 [0.15–1.00]; chemo, 0.39 [0.14–1.11]). Furthermore, pts who had pCR with NIVO + chemo had sustained OS improvement vs those without (HR [95% CI], 0.11 [0.04–0.36]; 5-y OS rates, 95% vs 56%). Neoadjuvant NIVO + chemo continued to improve EFS vs chemo (median [95% CI], 59.6 [31.6–NR] vs 21.1 mo [16.5–36.8]; HR [95% CI], 0.68 [0.51–0.91]); 5-y EFS rates were 49% vs 34%. No new safety signals were observed at this long-term f/u. Conclusions: CheckMate 816 is the only neoadjuvant-only immunotherapy phase 3 trial to demonstrate a statistically and clinically significant OS benefit at 5 y for a resectable solid tumor. Pts with pCR with neoadjuvant NIVO + chemo had a ~90% reduction in their risk of death by 5 y compared with those without pCR. The findings show long-term survival benefit from a short course of neoadjuvant NIVO + chemo and affirm a paradigm shift in the tx of resectable NSCLC without actionable genomic alterations. Clinical trial information: NCT02998528 . All pts PD-L1 < 1% PD-L1 ≥ 1% Stage IB/II Stage IIIA Squamous Non-squamous NIVO + chemo (N = 179) vs chemo (N = 179) NIVO + chemo (n = 78) vs chemo (n = 77) NIVO + chemo (n = 89) vs chemo (n = 89) NIVO + chemo (n = 65) vs chemo (n = 61) NIVO + chemo (n = 113) vs chemo (n = 116) NIVO + chemo (n = 87) vs chemo (n = 95) NIVO + chemo (n = 92) vs chemo (n = 84) Median OS, mo NR vs 73.7 NR vs 61.8 NR vs 73.7 NR vs 76.8 NR vs 73.7 NR vs 73.7 NR vs NR HR (95% CI) 0.72 (0.523–0.998) 0.89 (0.57–1.41) 0.51 (0.31–0.84) 0.77 (0.44–1.35) 0.70 (0.47–1.05) 0.71 (0.46–1.11) 0.72 (0.45–1.16)