PURPOSE: The miniature biodegradable implant siG12D-LODER™ was inserted into a 
tumor and released a siRNA drug against KRAS(G12D) along four months. This novel 
siRNA based drug was studied, in combination with chemotherapy, as targeted 
therapy for Locally Advanced Pancreatic Cancer (LAPC).
METHODS: An open-label Phase 1/2a study in the first-line setting of patients 
with non-operable LAPC was initiated. In this study patients were assigned to 
receive a single dose of siG12D-LODERs, in three escalating dose cohorts 
(0.025mg, 0.75mg and 3.0mg). Gemcitabine was given on a weekly basis, following 
the siG12D-LODERTM insertion, until disease progression. The recommended dose 
was further examined with modified FOLFIRINOX. The follow up period was eight 
weeks and survival until death.
RESULTS: Fifteen patients with LAPC were enrolled. Among the 15 treated 
patients, the most frequent adverse events observed were grade 1or 2 in severity 
(89%); five patients experienced serious adverse events (SAEs). In 12 patients 
analyzed by CT scans, none showed tumor progression, the majority (10/12) 
demonstrated stable disease and two showed partial response. Decrease in tumor 
marker CA19-9 was observed in 70% (7/10) of patients. Median overall survival 
was 15.12 months; 18 month survival was 38.5%.
CONCLUSIONS: The combination of siG12D-LODER™ and chemotherapy is well 
tolerated, safe and demonstrated a potential efficacy in patients with LAPC. 
NCT01188785.