KEY TAKEAWAYS
- The CheckMate 648 phase III trial aimed to present the initial comprehensive biomarker analysis findings from the CheckMate 648.
- The results confirmed the NIVO + chemo and NIVO + IPI efficacy in 1L ESCC, indicating improved OS across various biomarker subgroups.
In the CheckMate 648 trial, Nivolumab (NIVO) +chemotherapy (chemo) and NIVO + ipilimumab (IPI) outperformed chemo, securing approvals across multiple countries for previously untreated advanced esophageal squamous cell carcinoma (ESCC).
Ming Lei and the team conducted the study that aimed to present the initial findings of comprehensive exploratory biomarker analysis from this trial.
The study conducted whole exome sequencing (WES) on baseline tumor tissue and corresponding blood samples to evaluate tumor mutational burden (TMB) and identify specific gene alterations. TMB-high tumors were classified as having ≥ 199 mutations/exome. Additionally, RNA sequencing of baseline tumor tissue was performed to evaluate gene expression signatures (GES), with GES subgroups categorized based on signature score tertiles.
About 60% (191/321) of patients treated with NIVO + chemo were both WES- and GES-evaluable. Similarly, 62% (200/325) and 58% (188/325) of patients receiving NIVO + IPI, and 59% (190/324) and 59% (192/324) receiving chemo, respectively, were WES- and GES-evaluable. In the NIVO + chemo arm, patients with TMB-high tumors exhibited numerically longer median overall survival (mOS) compared with those with TMB-low tumors.
Conversely, mOS were comparable between TMB subgroups treated with NIVO + IPI, albeit the number of patients with TMB-high tumors was small. Higher inflammation and lower β-catenin GES scores correlated with better OS benefits of NIVO + chemo or IPI compared to chemo. Lower fibroblast GES scores were related to improved OS benefit of NIVO + IPI versus chemo. Additional biomarker analyses, including select gene alterations and GES in tumor cell PD-L1 subgroups, will be presented.
The findings supported the effectiveness of NIVO + chemo and NIVO + IPI in treating ESCC, indicating improved survival across various patient groups. Further validation in future trials is needed. Research was sponsored by Bristol-Myers Squibb.
Source: https://meetings.asco.org/abstracts-presentations/230563
Clinical Trial: https://clinicaltrials.gov/study/NCT03143153
Lei M, Doki Y, Kitagawa Y, et al. (2024). “Nivolumab (NIVO) plus (+) chemotherapy (chemo) or ipilimumab (IPI) vs chemo as 1L treatment for advanced esophageal squamous cell carcinoma (ESCC): First comprehensive biomarker analyses from CheckMate 648.” J Clin Oncol 42, 2024 (suppl 3; abstr 252) DOI: 10.1200/JCO.2024.42.3_suppl.252.
