OPDIVO is a human Immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor PD-1, with immune checkpoint inhibitory and antineoplastic activities. Currently, Bristol Myers Squibb is investigating the drug in the Phase III label expansion CheckMate 816 trial to demonstrate the benefit of neoadjuvant immunotherapy combined with chemotherapy, in a resectable lung cancer population.

During the ASCO 2025 conference, results of the CheckMate 816 trial, investigating safety and efficacy of the combination for resectable NSCLC, were presented. A total of 358 patients were concurrently assigned to receive combination or chemotherapy alone. The final analysis of overall survival significantly favored neoadjuvant OPDIVO plus chemotherapy over chemotherapy. At a median follow-up of 68.4 months, the 5-year overall survival was 65.4% with OPDIVO plus chemotherapy and 55% with chemotherapy alone, with consistency across most subgroups. In exploratory analyses, the 5-year overall survival in the OPDIVO-plus-chemotherapy group was 95.3% among the patients with a pathological complete response and 55.7% among those without such a response; survival was 75% among the patients with pre-surgery clearance of circulating tumor DNA (ctDNA) and 52.6% among those without such clearance.

In the nivolumab plus chemotherapy group, 94% of patients had adverse effects, with 43% being Grade 3–4. Treatment-related AEs (TRAEs) occurred in 84% (36% grade 3–4), and serious AEs (SAEs) in 17% (11% grade 3–4). Treatment-related SAEs affected 12%, with 8% being grade 3–4. Surgery-related AEs were seen in 45% (11% grade 3–4), and 10% discontinued due to TRAEs.

KOL insights

“The 4-year update showed that nivolumab plus chemotherapy had durable benefits despite the short course of treatment. This is statistically significant, as we have previously reported for EFS, and I would argue, clinically important, in terms of OS as opposed to chemotherapy alone, with improved lung cancer–specific survival. These improvements are occurring regardless of the type of platinum backbone utilized or the extent of surgical resection, sort of pointing to the fact that the surgeons need to extirpate all the disease by all means necessary in well-selected patients.” – Expert Opinion

“We are going to hear about the overall survival update for CheckMate 816, which was a Phase III study looking at chemoimmunotherapy in the neoadjuvant setting before patients go for surgical resection which is huge news to have that overall survival benefit for a neoadjuvant-only regimen.”  – Expert Opinion

Conclusion 

Chemotherapy was the cornerstone of treatment for advanced and metastatic NSCLC for many years; the advent of immune checkpoint inhibitors (ICIs) has transformed the therapeutic landscape. Among these, OPDIVO became the first immunotherapy to be approved for lung cancer in 2015, and its indications have since expanded to include neoadjuvant, adjuvant, and perioperative use. Despite OPDIVO's strong presence, it faces increasing competition from other ICIs such as KEYTRUDA, TECENTRIQ, and IMFINZI, which are also approved in various NSCLC settings. The competitive ICI landscape underscores the need for robust clinical evidence to support treatment decisions.

The CheckMate 816 trial has delivered compelling data in favor of OPDIVO, showing that three cycles of neoadjuvant OPDIVO plus chemotherapy significantly improved overall survival compared to chemotherapy alone in resectable NSCLC. With a 10% improvement in 5-year overall survival (65% vs. 55%) and a notable reduction in lung cancer-specific mortality, these results provide strong validation for OPDIVO's role in early-stage disease. This trial positions OPDIVO as a leading immunotherapy option in the neoadjuvant setting and strengthens its competitive edge in the increasingly crowded NSCLC treatment landscape.