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0A recent phase 1/2 clinical trial investigated the safety and efficacy of combining the selective KRAS G12D inhibitor HRS-4642 with the PD-L1 immunotherapy adebrelimab in heavily pretreated patients suffering from metastatic pancreatic ductal adenocarcinoma (PDAC). The chemotherapy-free combination demonstrated a manageable safety profile with zero treatment-related deaths, while achieving a confirmed objective response rate of 43.2% and a disease control rate of 81.1% in the recommended phase 2 dose cohort. Furthermore, exploratory circulating tumor DNA (ctDNA) analyses indicated that tracking KRAS G12D variant allele frequencies could effectively serve as a predictive biomarker for monitoring therapeutic response and identifying the emergence of acquired resistance.
References:
Shi S, Wei M, Du N, et al. Chemotherapy-free phase 1/2 trial of HRS-4642 plus adebrelimab in previously treated metastatic KRAS G12D-mutant pancreatic cancer[J]. Cancer Cell, 2026.
