CheckMate 816 Shows OS Benefit in Resectable NSCLC With 5-Year Follow-Up

CheckMate 816 is now the “only neoadjuvant-only immunotherapy phase 3 trial to demonstrate a statistically and clinically significant” 5-year overall survival (OS) benefit for a resectable solid tumor, according to a presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

Patrick M. Forde, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, presented the late-breaking abstract during an oral abstract session at the 2025 ASCO Annual Meeting.

The combination of nivolumab plus chemotherapy is an “established standard of care neoadjuvant treatment” for eligible patients with resectable non-small cell lung cancer (NSCLC) and previously showed “statistically significant and clinically meaningful improvements” in event-free survival (EFS) and pathological complete response in the phase 3 CheckMate 816 study.

At the 2025 ASCO Annual Meeting, Dr. Forde reported the planned final analysis of OS data from CheckMate 816 with 5 years of follow-up.

The trial included adults with stage IB-IIIA resectable NSCLC, Eastern Cooperative Oncology Group performance status of ≤ 1, and no known EGFR or ALK alterations. Patients were randomized 1:1 to receive neoadjuvant nivolumab plus chemotherapy Q3W or chemotherapy alone Q3W for three cycles, followed by surgery.

The primary endpoints of CheckMate 816 were EFS and pCR, both assessed by blinded independent review. OS was a key prespecified, statistically powered secondary endpoint that was tested hierarchically, with exploratory analyses included for OS by ctDNA clearance and pCR status.

CheckMate 816 Overall Survival Outcomes With Neoadjuvant Nivolumab plus Chemotherapy

With a median follow-up of 68 months, the neoadjuvant nivolumab plus chemotherapy regimen demonstrated a statistically significant OS benefit compared with chemotherapy alone (median [95% CI], not reached [NR] versus 73.7 months [47.3–NR]; HR [95% CI], 0.72 [0.523–0.998]; P = 0.0479). The 5-year OS rate was 65% in those receiving the combination regimen, compared with 55% in those receiving chemotherapy alone. The OS “favored” the combination regimen in the subgroups of patients that were defined by tumor PD-L1 expression, baseline disease stage, and histology.

Coral Olazagasti, MD, of the Sylvester Comprehensive Cancer Center and the University of Miami Miller School of Medicine, shared her reaction to the long-awaited OS data from CheckMate 816.

“Whenever EFS benefits translate into an overall survival benefit, then it’s something that we can confirm,” she said. “We can feel secure that this regimen works.”

An exploratory analysis of patients who were positive for ctDNA at baseline included 43 patients from each treatment group. The exploratory analysis showed that patients with presurgical ctDNA clearance, including 56% of those receiving the combination regimen and 35% of those receiving chemotherapy alone, had “continued OS improvement” compared with those without presurgical ctDNA across both treatment arms (HR [95% CI]: NIVO + chemo, 0.38 [0.15–1.00]; chemo, 0.39 [0.14–1.11]). Patients who achieved a complete pathologic response with nivolumab plus chemotherapy experienced “sustained OS improvement” compared to those who did not (HR [95% CI], 0.11 [0.04–0.36]), with 5-year OS rates of 95% versus 56%.

In addition, neoadjuvant nivolumab plus chemotherapy continued to improve EFS compared with chemotherapy, showing a median EFS of 59.6 months (95% CI, 31.6–NR) compared with 21.1 months (95% CI, 16.5–36.8; HR [95% CI], 0.68 [0.51–0.91]). The five-year EFS rates were 49% in the group receiving the combination therapy versus 34% in those receiving chemotherapy alone. The researchers reported that “no new safety signals were observed” in this long-term follow-up analysis.

Based on these findings, the study authors concluded that patients with a complete pathologic response to neoadjuvant nivolumab plus chemotherapy had a ~90% reduction in their risk of death by five years compared with those who did not have a complete pathologic response, and that these findings show a “long-term survival benefit from a short course” of neoadjuvant nivolumab plus chemotherapy and “affirm a paradigm shift” in the treatment of resectable NSCLC without actionable genomic alterations.