RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients

摘要: // Talia Golan 1 , Elina Zorde Khvalevsky 2 Ayala Hubert 3 Rachel Malka Gabai Naama Hen Amiel Segal 4 Abraham Domb 5 Gil Harari 6 Eliel Ben David 7 Stephen Raskin Yuri Goldes Eran Goldin 8 Rami Eliakim Maor Lahav Yael Kopleman 9 Alain Dancour Amotz Shemi and Eithan Galun 10 The Sackler School of Medicine, Chaim Sheba Medical Center, Tel Aviv University, Aviv, Israel Silenseed Ltd., Jerusalem, Sharett Institute Oncology, Hadassah-Hebrew University Gastroenterology Institute, Shaare Zedek Centre, Drug Research, Pharmacy-Faculty Center for Nanoscience Nanotechnology Alex Grass Centre Design Synthesis, Hebrew MediStat Hadassah Goldyne Savad Gene Therapy, Correspondence to: Golan, email: Keywords : Pancreatic cancer, KRAS, overall survival, siRNA, polymer implant Received March 04, 2015 Accepted May 02, Published 19, Abstract Purpose: miniature biodegradable siG12D-LODER™ was inserted into a tumor released siRNA drug against KRAS(G12D) along four months. This novel based studied, in combination with chemotherapy, as targeted therapy Locally Advanced Cancer (LAPC). Methods: An open-label Phase 1/2a study the first-line setting patients non-operable LAPC initiated. In this were assigned to receive single dose siG12D-LODERs three escalating cohorts (0.025mg, 0.75mg 3.0mg). Gemcitabine given on weekly basis, following siG12D-LODER TM insertion, until disease progression. recommended further examined modified FOLFIRINOX. follow up period eight weeks survival death. Results: Fifteen enrolled. Among 15 treated patients, most frequent adverse events observed grade 1or severity (89%); five experienced serious (SAEs). 12 analyzed by CT scans, none showed progression, majority (10/12) demonstrated stable two partial response. Decrease marker CA19-9 70% (7/10) patients. Median 15.12 months; 18 month 38.5%. Conclusions: chemotherapy is well tolerated, safe potential efficacy LAPC. NCT01188785