Phase III CheckMate -816 trial of neoadjuvant Opdivo + chemo shows sustained benefits in NSCLC at 3 year follow-up, as presented at ELCC

With median follow up of 41.4 months, Opdivo with chemotherapy reduced the risk of disease recurrence, progression or death by 32%, demonstrating a landmark three-year event-free survival (EFS) rate of 57% with Opdivo with chemotherapy compared to 43% with chemotherapy alone (Hazard Ratio [HR], 0.68; 95% Confidence Interval [CI], 0.49 to 0.93). Additionally, time to distant metastasis or death (TTDM), defined as the time between the date of randomization and the first date of distant metastasis or the date of death in the absence of distant metastasis, continued to favor Opdivo with chemotherapy compared to chemotherapy alone (HR, 0.55; 95% CI, 0.39 to 0.78), with three-year landmark TTDM rates of 71% vs. 50%, respectively.

While overall survival (OS) remained immature at this analysis, there was a continued encouraging trend in OS favoring neoadjuvant Opdivo with chemotherapy over chemotherapy alone (HR 0.62; 99.34% CI: 0.36 to 1.05). At three years, 78% of patients treated with neoadjuvant Opdivo and chemotherapy were alive, compared to 64% with chemotherapy alone. OS will continue to be followed for upcoming analyses.

Exploratory analyses included EFS by surgical approach, EFS by extent or completeness of resection, and EFS and pathologic complete response (pCR) by a four-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score derived from RNA sequencing of baseline tumor samples. Opdivo with chemotherapy continues to demonstrate improved EFS benefit at three years vs. chemotherapy in patients who had surgery, regardless of surgical approach or extent of resection, and in patients with R0 resection. In the Opdivo with chemotherapy arm, baseline four-gene inflammatory signature scores were numerically higher in patients with pCR compared to patients without and patients with higher baseline inflammatory scores appeared to have improved EFS with the combination, relative to those with lower scores. After three years of follow up, the safety profile of neoadjuvant Opdivo with chemotherapy was consistent with the primary analysis, with no new safety signals observed. Grade 3-4 treatment-related and surgery-related adverse events occurred in 36% and 11% of patients in the Opdivo with chemotherapy arm, respectively, vs. 38% and 15% in the chemotherapy arm, respectively.

These updated results will be featured in a proffered paper oral session at the European Lung Cancer Congress (ELCC) 2023 from March 29-April 1, 2023.