Discovery of Predictive Circulating Proteomic Biomarkers for Therapy Response in HRR-Driven Solid Tumors

The IMAGENE trial (jRCT2051210120) is a multicenter, tumor-agnostic, phase II basket study evaluating the combination of the PARP inhibitor niraparib and PD-1 inhibitors in patients with homologous recombination repair (HRR) gene mutations who have progressed following prior immune checkpoint inhibitor (ICI) therapy. In this tumor-agnostic setting, patients were enrolled with unresectable, locally advanced urothelial carcinoma (UC), renal cell carcinoma (RCC), gastric cancer (GC), esophageal cancer (EC), head and neck cancer (HNC), and melanoma (MC), all harboring HRR gene alterations. A total of 45 patients were enrolled in the primary cohort between April 2022 and April 2024.

Existing biomarkers such as PD-L1 expression and tumor mutation burden (TMB) have shown limited predictive power in ICI-treated and HRR-driven tumors. To address this gap, we performed unbiased deep plasma proteomic profiling, complemented by a targeted inflammatory marker panel (NULISA inflammation panel), on baseline and on-treatment samples from HNC participants enrolled in the IMAGENE trial.