KEY TAKEAWAYS
- The phase 2 trial aimed to assess VIGex and other biomarkers in patients treated with pembrolizumab from INSPIRE.
- The data indicated that adding ΔctDNA to baseline VIGex could improve predictions for immunotherapy outcomes.
Immune gene expression signatures are emerging as potential biomarkers for immunotherapy. VIGex, a 12-gene expression classifier developed using both nCounter (Nanostring) and RNA sequencing (RNA-seq) assays, has been analytically validated across laboratories. It categorizes tumor samples into hot, intermediate-cold (I-Cold), and cold subgroups. VIGex-Hot has been linked to improved outcomes with immunotherapy.
Alberto Hernando-Calvo and the team aimed to assess the performance of VIGex and other immunotherapy biomarkers in a dataset of patients treated with pembrolizumab from the INSPIRE Phase II trial.
Patients with advanced solid tumors received 200 mg of pembrolizumab intravenously every 3 weeks. Tumor RNA-seq data from baseline samples were analyzed using the VIGex algorithm. Circulating tumor DNA (ctDNA) was measured at baseline and at the start of cycle 3 using the Signatera assay. VIGex-Hot was compared with VIGex I-Cold + Cold, and 4 groups were defined based on VIGex subgroups and changes in ctDNA (ΔctDNA) from baseline to cycle 3.
About 76 patients patients were enrolled, including 16 with ovarian cancer, 12 with breast cancer, 12 with head and neck cancers, 10 with melanoma, and 26 with other tumor types. The objective response rate (ORR) was 24% for VIGex-Hot and 10% for I-Cold/Cold. The VIGex-Hot subgroup showed better overall survival (OS) and progression-free survival (PFS) in a multivariable model adjusted for tumor type, tumor mutation burden, and PD-L1 immunohistochemistry. Adding ΔctDNA enhanced the predictive accuracy of baseline VIGex classification for both OS and PFS.
The data indicated that adding ΔctDNA to baseline VIGex may enhance the prediction of immunotherapy outcomes.
The trial was sponsored by University Health Network, Toronto.
Source: https://pubmed.ncbi.nlm.nih.gov/39178369/
Clinical Trial: https://clinicaltrials.gov/study/NCT02644369
Hernando-Calvo A, Yang SYC, Vila-Casadesús M, et al. (2024). “Combined Transcriptome and Circulating Tumor DNA Longitudinal Biomarker Analysis Associates With Clinical Outcomes in Advanced Solid Tumors Treated With Pembrolizumab.” JCO Precis Oncol. 2024;8:e2400100. doi:10.1200/PO.24.00100
