Phase I clinical development of Atu027, a siRNA formulation targeting PKN3 in patients with advanced solid tumors

RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions

“…In a phase 1 study in patients with solid tumors, Atu027 was shown to be well tolerated and caused disease stabilization in 52% of patients including 1 patient who experienced complete regression of pulmonary lesions. 107 More recently, a post hoc analysis of data from a phase 1b/2a trial of Atu027 in combination with standard gemcitabine treatment in patients with advanced or metastatic pancreatic adenocarcinoma demonstrated a statistically significant increase in progression-free survival in the Atu027 arm. 108 The siRNA siG12D, which is selective for mutant KRAS (KRASG12D mutation), is encapsulated in a biodegradable polymer Local Drug Eluter (LODER) for controlled and prolonged delivery.…”

RNAi-based Cancer Therapeutics: Are we there yet?

“…Currently, there are many clinical trials in progress, most of them in Phase-I/IIa, evaluating the safety and efficacy of such siRNA-based drugs for cancer therapeutics [40][41][42][43][44]. The detailed description of the various ongoing current clinical trial programs is mentioned in Table 1.…”

“…Various promising nanoparticles (NPs) strategies that have been successful in depicting in vitro gene silencing and tumor reduction efficacy in animal models, safety in non-human primates and in few cases, have undergone clinical trial testing include, (A) Lipid based NPs: liposomes [16], lipoplexes [17,18], stable nucleic acid lipid nanoparticles (SNALP) [19,20] & lipidoid [21], polycation liposomes [22,23], (B) Polymeric NPs: both natural and synthetic, includes cyclodextrin [24], chitosan [25], PLGA [26], polymeric micelles [27], PEI [28] & dendrimers [29], (C) Inorganic NPs: calcium phosphate CaP [30], (D) Carbon-based materials, carbon nanotubes (SWNTs, MWNTs) [31,32], (E) Metal nanoparticles -Gold (Au) [33], Quantum dots (QDs) [34], silicon-based nanoparticles (MSNPs) [35] & super paramagnetic iron oxide nanoparticles (SPIONs) [36] etc. In addition to this, atelocollagen-based delivery strategy also proved to be successful in few cases [37,38].…”

Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells

“…However in order to translate RNAi into clinical use effective non-toxic delivery systems are essential. The development of novel biomaterials has facilitated the formulation of multifunctional nanoparticles (NPs) to deliver siRNA and these have been investigated in the treatment of both solid tumours and leukaemia [9] [10] [11].…”