Perioperative nivolumab (NIVO) vs placebo (PBO) in patients (pts) with resectable NSCLC: Updated survival and biomarker analyses from CheckMate 77T.

Abstract

LBA8010 Background: The phase 3 CheckMate 77T study demonstrated statistically significant and clinically meaningful improvement in EFS with perioperative NIVO vs PBO in pts with resectable NSCLC. pCR rates were also improved. Here, we report updated EFS, OS from the first prespecified interim analysis, and exploratory biomarker analyses. Methods: Pts with resectable stage IIA–IIIB (N2; AJCC v8) NSCLC were randomized 1:1 to neoadjuvant (neoadj) NIVO + chemotherapy (chemo) Q3W (up to 4 cycles [cyc]) followed by adjuvant (adj) NIVO Q4W (up to 13 cyc) or neoadj PBO + chemo Q3W (up to 4 cyc) followed by adj PBO Q4W (up to 13 cyc). The primary endpoint was EFS per BICR. Secondary endpoints included pCR, OS, and safety. Exploratory analyses included efficacy by pCR status, presurgery ctDNA clearance (CL), and tumor genomic alterations. Results: At a median follow-up of 41.0 mo (database lock, 16 Dec 2024), NIVO continued to provide EFS benefit vs PBO (HR [95% CI], 0.61 [0.46–0.80]; 30-mo EFS rates, 61% vs 43%) in all randomized pts and regardless of disease stage, tumor histology, or PD-L1 expression (Table). EFS from surgery (HR [95% CI]) continued to favor NIVO vs PBO in pts with pCR (0.90 [0.19–4.15]) or without (w/o; 0.72 [0.50–1.05]). In biomarker-evaluable pts (NIVO, 98; PBO, 92), pts with ctDNA CL had greater EFS benefit (assessed from randomization) vs pts w/o (HR [95% CI]: NIVO, 0.41 [0.20–0.86]; PBO, 0.62 [0.31–1.22]); pts with ctDNA CL with or w/o pCR had improved EFS vs pts w/o ctDNA CL and pCR (data to be presented). EFS (HR [95% CI]) favored NIVO vs PBO in pts with tumor genomic alterations ( KRAS , and/or STK11 , and/or KEAP1 mutations; 0.63 [0.32–1.23]) or w/o (0.65 [0.39–1.10]). Higher ctDNA CL and pCR rates were seen with NIVO vs PBO regardless of mutation status; additional efficacy and ctDNA outcomes will be presented. At the first prespecified interim OS analysis, NIVO showed a trend of OS improvement vs PBO in all randomized pts (HR [97.63% CI], 0.85 [0.58–1.25]; median OS, not reached in both tx arms; 30-mo OS rates, 78% vs 72%). Safety outcomes were consistent with previous reports. Conclusions: In this update, perioperative NIVO continued to show long-term EFS benefit and a favorable OS trend vs PBO in pts with resectable NSCLC; no new safety signals were observed. In exploratory analyses, presurgery ctDNA CL was associated with EFS benefit. EFS favored NIVO vs PBO regardless of KRAS , STK11 , and KEAP1 mutation status. Clinical trial information: NCT04025879 . All pts Stage II Stage III Squamous Non-squamous PD-L1 < 1% PD-L1 ≥ 1% NIVO (N = 229) vs PBO(N = 232) NIVO (n = 80) vs PBO(n = 81) NIVO (n = 149) vs PBO(n = 149) NIVO (n = 116) vs PBO(n = 118) NIVO (n = 113) vs PBO(n = 114) NIVO (n = 93) vs PBO(n = 93) NIVO (n = 128) vs PBO(n = 128) Median EFS, mo 46.6 vs 16.9 NR vs NR 42.1 vs 13.4 NR vs 16.4 40.1 vs 16.9 40.1 vs 19.8 46.6 vs 15.1 HR (95% CI) 0.61(0.46–0.80) 0.77(0.46–1.30) 0.54(0.39–0.74) 0.53(0.35–0.80) 0.69 (0.48–1.00) 0.79(0.52–1.21) 0.53(0.36–0.76)