Clinical Research Papers:
RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients
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Talia Golan1, Elina Zorde Khvalevsky2, Ayala Hubert3, Rachel Malka Gabai2, Naama Hen2, Amiel Segal4, Abraham Domb5, Gil Harari6, Eliel Ben David7, Stephen Raskin1, Yuri Goldes1, Eran Goldin8, Rami Eliakim1, Maor Lahav1, Yael Kopleman9, Alain Dancour8, Amotz Shemi2 and Eithan Galun10
1 The Sackler School of Medicine, The Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
2 Silenseed Ltd., Jerusalem, Israel
3 Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
4 The Gastroenterology Institute, Shaare Zedek Medical Centre, Jerusalem, Israel
5 Institute of Drug Research, School of Pharmacy-Faculty of Medicine, Center for Nanoscience and Nanotechnology and The Alex Grass Centre for Drug Design and Synthesis, The Hebrew University of Jerusalem, Jerusalem, Israel
6 MediStat Ltd., Jerusalem, Israel
7 Hadassah-Hebrew University Medical Centre, Jerusalem, Israel
8 The Gastroenterology Institute, Shaare Zedek Medical Center, Jerusalem, Israel
9 Gastroenterology Institute, Hadassah Hebrew University Medical Center, Jerusalem, Israel
10 The Goldyne Savad Institute for Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel
Talia Golan, email:
Keywords: Pancreatic cancer, KRAS, overall survival, siRNA, polymer implant
Received: March 04, 2015 Accepted: May 02, 2015 Published: May 19, 2015
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
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