Phase I Study Results of pbi-shRNA™ STMN1 Nanoplex Via Intratumoral Injection in Advanced Cancer
John Nemunaitis, Minal Barve, Zhaohui Wang, F. C. Brunicardi, Nancy S. Templeton, Neil Senzer, Padmasini Kumar, Gladice Wallraven, Chris M. Jay, Joseph Kuhn, Peter Beitsch, Robert G. Mennel, Haskell M. Kirkpatrick, Douglas Orr, Scott Stone, Tammy Roque, Phillip B. Maples, Donald D. Rao. Mary Crowley Cancer Research Centers, Dallas, TX; Medical City Dallas Hospital, Dallas, TX; Texas Oncology, P.A., Dallas, TX; Gradalis, Inc., Dallas, TX; WLS Surgical Associates, P.A., Dallas, TX; David Geffen School of Medicine at UCLA, Los Angeles, CA; Strike Bio, Inc., Dallas, TX
STMN1 is a microtubule destabilizing protein critical in the control of mitosis and is differentially overexpressed in malignant versus non-malignant tissue. Using our novel RNA interference construct, pbi-shRNA™-STMN1 nanoplex, we previously demonstrated STMN1 expression knockdown in surgically obtained human tumors as well as safety and efficacy in animal xenograft and tumor graft models thereby justifying Phase I testing (BB-IND 14938).
Eleven patients (angiosarcoma, anal, colorectal, sarcoma, head and neck, ovarian, melanoma x2 and breast cancer x3) have entered into our dose-escalation trial. Design is shown in Figure 1. PK analyses of circulating plasmid of evaluable patients in cohorts 1 and 2 is shown in Figure 2. No toxic effects were observed. All patients demonstrated stable disease during the first month post-treatment. Intratumoral cleavage product was demonstrated in cohorts 1 and 2 by next generation sequencing and by RLM RACE assay in cohort 3.
These results support continuation of Phase I testing and establish the basis for transition to systemic treatment starting at a dose level equivalent to demonstrated safe plasmid levels in circulation.
Keywords: Cancer Gene Therapy; Non-Viral Gene Delivery; RNAi and shRNA
Session: Poster Session: Cancer-Targeted Gene and Cell Therapy: Non-Viral Approaches, and Screening/New Target Identification (5:15 PM-7:15 PM)
Date/Time: Friday, May 23, 2014 - 5:15 PM
Room: Hall A and B South