Engineered exosomes with Kras^G12D specific siRNA in pancreatic cancer: a phase I study with immunological correlates.

ABSTRACT: Oncogenic KRAS is amongst the key genetic drivers for initiation and maintenance of pancreatic ductal adenocarcinoma (PDAC). Here, we show that engineered exosomes with Kras^G12D specific siRNA (iExoKras^G12D) reveal a biodistribution in pancreas with negligible toxicity in preclinical studies in mice and Rhesus macaques. Clinical testing of iExoKras^G12D in the iEXPLORE (iExoKras^G12D in Pancreatic Cancer) Phase I study employed a non-randomized single-arm classical 3 + 3 dose escalation design (Phase Ia), followed by an accelerated titration design (Phase Ib) (NCT03608631). The primary outcomes included safety, tolerability and target engagement, and the secondary outcomes aimed to assess disease control. Patients with advanced metastatic disease w

SUBMITTER: Kalluri VS 

PROVIDER: S-EPMC12485160 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature