Nivolumab Extends EFS Across Resectable NSCLC Subgroups

“Perioperative nivolumab improved EFS across all analyzed subgroups. Results of these efficacy and biomarker analyses further support perioperative nivolumab as an efficacious treatment option for patients with resectable NSCLC,” according to senior study author Mariano Provencio, MD, PhD.

Regardless of the presence of KRAS, STK11, and/or KEAP1 mutations, patients with resectable non–small cell lung cancer (NSCLC) experienced an event-free survival (EFS) benefit with perioperative nivolumab (Opdivo) compared with placebo, according to a presentation on updated findings from the phase 3 CheckMate-77T trial (NCT04025879) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.1

At a median follow-up of 41.0 months (range, 31.3-59.8), the median EFS was 46.6 months (95% CI, 35.8-not reached [NR]) with nivolumab (n = 229) vs 16.9 months (95% CI, 13.6-28.2) with placebo (n = 232; HR, 0.61; 95% CI, 0.46-0.80). The 24- and 30-month EFS rates according to blinded independent central review (BICR) were 67% and 61% with nivolumab, respectively, vs 44% and 43% with placebo.

“Perioperative nivolumab improved EFS across all analyzed subgroups. Results of these efficacy and biomarker analyses further support perioperative nivolumab as an efficacious treatment option for patients with resectable NSCLC,” senior study author Mariano Provencio, MD, PhD, chair of the Department of Medical Oncology at Hospital Universitario Puerta de Hierro, in Madrid, Spain, said in a presentation of the data.

CheckMate-77T: Trial Design, Prior Findings, and a Pivotal Approval

CheckMate-77T was a double-blind study that enrolled patients with resectable stage IIA to IIIB NSCLC per AJCC 8th Edition staging criteria who received no prior systemic anticancer therapy, had an ECOG performance status of 0 or 1, and did not have EGFR mutations or known ALK alterations.2

Eligible patients were randomly assigned 1:1 to receive nivolumab at a dose of 360 mg or placebo every 3 weeks, both in combination with chemotherapy every 3 weeks for up to 4 cycles. Both groups then underwent surgery followed by adjuvant nivolumab at a dose of 480 mg every 4 weeks or placebo at the same dosing schedule, both for up to 1 year.

The primary end point was EFS by BICR per RECIST 1.1 criteria. Secondary end points included pathologic complete response (pCR) and major pathologic response rates by blinded independent pathologic review, as well as overall survival (OS) and safety.

In October 2024, the FDA approved nivolumab plus platinum-doublet chemotherapy as neoadjuvant treatment, followed by single-agent nivolumab after surgery as adjuvant treatment, for adults with resectable (tumors ≥ 4 cm and/or node positive) NSCLC and no known EGFR mutations or ALK rearrangements.3 The approval was based on earlier data from CheckMate-77T showing a statistically significant and clinically meaningful improvement in EFS with the regimen vs placebo (HR, 0.58; 95% CI, 0.43-0.78; P = .00025).

Additional Efficacy Data According to ctDNA Clearance, pCR, and Mutation Status

Additional EFS analyses by tumor mutation status demonstrated similar improvements in patients with and without KRAS, KEAP1, or STK11 mutations.1 A total of 190 patients had biomarker-evaluable samples in the nivolumab (n = 98) and placebo (n = 92) arms. Mutations were found solely in KEAP1 (11%), KRAS (13%), and STK11 (5%), in KEAP1 and KRAS (2%), KRAS and STK11 (4%), and all 3 (2%).

Within the mutated subgroup, the median EFS was 28.9 months (95% CI, 13.2-NR) with nivolumab (n = 33) vs 10.5 months (95% CI, 8.8-31.4) with placebo (n = 34; HR, 0.63; 95% CI, 0.32-1.23). In the wild-type subgroup, the median EFS was NR (95% CI, 29.0-NR) with nivolumab (n = 65) vs 17.0 months (95% CI, 10.8-NR) with placebo (n = 58; HR, 0.65; 95% CI, 0.39-1.10).

EFS was also evaluated through the lens of circulating tumor ctDNA (ctDNA) and pCR status. A total of 66% (n = 50) of patients who received nivolumab (n = 76) cleared their ctDNA vs 38% (n = 24) of patients who received placebo (n = 64). Fifty percent (n = 25) of patients who cleared their ctDNA in the nivolumab arm (n = 50) achieved pCR vs 12% (n = 3) of those who cleared their ctDNA in the placebo arm (n = 24). Regarding patients who cleared their ctDNA in the nivolumab (n = 50) and placebo arms (n = 24), 50% (n = 25) and 88% (n = 21) did not achieve pCR, respectively.

Provencio noted that almost all patients in the placebo arm who did not clear their ctDNA (n = 40; 62%) did not experience pCR either (n = 39; 98%).

Within the nivolumab arm, patients who achieved ctDNA clearance and pCR had improved EFS vs those who achieved ctDNA clearance but not pCR (HR, 0.29; 95% CI, 0.10-0.85) and those who achieved neither ctDNA clearance nor pCR (HR, 0.23; 95% CI, 0.08-0.65). Within the placebo arm, patients who achieved ctDNA clearance but not pCR had improved EFS outcomes vs those who achieved neither ctDNA clearance nor pCR (HR, 0.77; 95% CI, 0.39-1.54). Outcomes were not calculable between patients who achieved both ctDNA clearance and pCR and those who achieved ctDNA clearance but not pCR, or neither ctDNA clearance nor pCR.

“ctDNA clearance and pCR were associated with improved EFS, regardless of treatment,” Provencio explained.

A first look at OS revealed that the significance boundary was not met, although a trend was seen in favor of nivolumab. The median OS was NR in either the nivolumab or placebo arm (HR, 0.85; 97.63% CI, 0.58-1.25). The 24- and 30-month OS rates were 80% and 78% with nivolumab, respectively, vs 77% and 72% with placebo.

The median lung cancer–specific survival (LCSS) was also NR in either arm (HR, 0.60; 95% CI, 0.40-0.89). The 24- and 30-month LCSS rates were 89% and 87% with nivolumab, respectively, vs 80% and 75% with placebo.

A Glimpse Into Safety

Regarding safety in the nivolumab arm (n = 228), most patients experienced adverse effects (AEs; any grade, 97%; grade 3/4, 47%) and treatment-related AEs (TRAEs; 89%; 32%). AEs (25%; 14%) and TRAEs (19%; 11%) leading to discontinuation also occurred. Serious AEs (42%; 28%) and serious TRAEs (19%; 14%) were also reported. No new surgery-related AEs or treatment-related deaths had occurred since the two reported prior to the database lock, Provencio said.

“No new safety signals were observed at this clinical update,” Provencio said.

Disclosures: Provencio listed honoraria from AstraZeneca, Bristol-Myers Squibb, Janssen, Lilly, MSD, Pfizer, Roche, and Takeda; consulting or advisory roles with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Gilead Sciences, Guardant Health, Incyte, Ipsen, Janssen Oncology, Johnson & Johnson, Lilly, Merck, MSD, Pfizer, Roche, and Takeda; speakers’ bureau for Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Johnson & Johnson/Janssen, Lilly, MSD, Pfizer, Roche, and Takeda; research funding from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Pfizer, Pierre Fabre, Roche, and Takeda; and travel expenses from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Lilly, MSD, Pfizer, Pierre Fabre, Roche, and Takeda; and other relationship with Pfizer.

References

1. Cascone T, Awad M, Spicer J, et al. Perioperative nivolumab (NIVO) vs placebo (PBO) in patients (pts) with resectable NSCLC: Updated survival and biomarker analyses from CheckMate 77T. J Clin Oncol. 2025;43(suppl 17):LBA8010. doi:10.1200/JCO.2025.43.17_suppl.8010
2. Cascone T, Awad MM, Spicer JD, et al. CheckMate 77T: phase III study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage II–IIIb NSCLC. Ann Oncol. 2023;34(suppl 2):1295. doi:10.1016/j.annonc.2023.10.050
3. FDA approves neoadjuvant/adjuvant nivolumab for resectable non-small cell lung cancer. FDA. October 3, 2024. Accessed June 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-nivolumab-resectable-non-small-cell-lung-cancer