. Author manuscript; available in PMC: 2017 Apr 1.

Published in final edited form as: Cancer Treat Rev. 2016 Feb 22;45:19–29. doi: 10.1016/j.ctrv.2016.02.005

Table 1. Clinical Trials of nanoparticle-mediated siRNA delivery upon systemic administration for cancer treatment.

The drug names, companies, material descriptions, targeted diseases, and their clinical status are shown.

Drug	Company	Gene target	Description	Diseases/Indications	Clinical status (Trial number)	Outcomes/Limitations
CALAA-01^{41, 77}	Calando Pharma	RRM2	Cyclodextrin-based nanoparticles with transferrin as a targeting agent	Solid tumor/advanced melanoma	Phase I, terminated (NCT00689065)	Stable disease observed in one (out of three) patient; biopsies show successful gene knockdown. However, construct is rapidly destabilized in kidneys⁷⁸ and could explain adverse events in patients (e.g., liver/kidney toxicity, platelet drop, prolonged APPT), which were also found in animals receiving the polymer delivery components alone.
ALN-VSP02⁴²	Alnylam Pharma	KSP + VEGF	Stable nucleic acid lipid particles (SNALPs)	Advanced solid tumors with liver involvement	Phase I, completed (NCT00882180)	4 out of 24 patients receiving >0.7 mg/kg achieved stable disease, 1 of which achieved complete response. One patient died from liver failure possibly from disease progression and/or drug-induced injury to the small amount of remaining normal liver. Phase II will establish pharmacodynamics changes and clinical outcome.
ALN-VSP02⁴²	Alnylam Pharma	KSP + VEGF	Stable nucleic acid lipid particles (SNALPs)	Advanced solid tumors with liver involvement	Phase I, completed (NCT01158079)
Atu027^{79, 80}	Silence Therapeutics	PKN3	Cationic lipoplex containing siRNA	Advanced solid tumors	Phase I, completed (NCT00938574)	In phase I, 14 out of 34 patients had stable disease. Given with gemcitabine, Phase IIa data indicated that higher and more frequent doses needed to be investigated prior to full Phase II study.
Atu027^{79, 80}	Silence Therapeutics	PKN3	Cationic lipoplex containing siRNA	Pancreatic ductal carcinoma	Phase I/II, ongoing (NCT01808638)
TKM-080301⁸¹	Tekmira Pharma (now called Arbutus Biopharma)	PLK1	Stable nucleic acid lipid particles (SNALPs)	Solid tumors with liver involvement	Phase I, completed (NCT01437007)	Stable disease (4/9) if >0.6 mg/kg, but max tolerated dose = 0.75 mg/kg.
				Neuroendocrine tumors and adrenocortical carcinoma	Phase I/II, completed (NCT01262235)	Outcomes are not available yet.
				Hepatocellular carcinoma (HCC)	Phase I/II, ongoing (NCT02191878)	Phase IIa clinical trial has also been modified to treat chronic HBV patients enrolled in the HCC trial
DCR-MYC⁸²	Dicerna Pharma	MYC	Lipid nanoparticles	Solid tumors, myeloma and lymphoma	Phase I, recruiting (NCT02110563)	Interim data report mild adverse events, and some metabolic response and tumor shrinkage.⁸³
DCR-MYC⁸²	Dicerna Pharma	MYC	Lipid nanoparticles	Hepatocellular carcinoma	Phase I/II, recruiting (NCT02314052)	Recruiting, no published result yet
siRNA-EphA2-DOPC⁸⁴	MD Anderson Cancer Center	EphA2	Neutral liposomes	Advanced cancer	Phase I, recruiting (NCT01591356)	Liposome without targeting agent (Recruiting)