Table 3.

Drug levels and changes in target mRNA in tumor biopsies after first dose

Postdose biopsy, %Drug levelsa (ng/g tissue)Change in target mRNA (qRT- PCR)
Patient no.Dose, mg/kgTumor type (biopsy site, day of postdose biopsy)Viable tumorLiverFibrosis/necrosisVEGF siRNAKSP siRNAVEGF mRNAKSP mRNA
0070.40Colorectal (liver, d7)1780325.712.520%↓eNo Δ
0170.40Ovarian (liver, d2)095528.917.2N/AN/A
0190.70Colorectal (liver, d2)2057514273.3No ΔNo Δ
0221.00Colorectal (adrenal, d2)10078b9.83.8No ΔNo Δ
0251.00Sarcoma (muscle, d2)96040.450.40No ΔNo Δ
0331.00Colorectal (liver, d3)56035c5.42.2No ΔNo Δ
0411.00Renal td (liver, d2)7015156.06.8No ΔNo Δ
0421.00Uveal melanoma (liver, d2)100007.05.8No ΔNo Δ
0261.25Colorectal (liver, d6)14071d0.32<LLOQNo ΔNo Δ
0311.25Ovarian (abdomen, d4)300704.93.674%↓eNo Δ
0351.25Ovarian (lymph node, d5)4006020.420.337%↓e25%↓e
0321.50Small bowel (liver, d6)420584.93.6No ΔNo Δ

NOTE: N/A indicates no sample for analysis.

  • aMeasured by qRT-PCR, LLOQ (lower limit of quantitation) = 0.14 ng/g tissue. All pretreatment biopsy samples were <LLOQ.

  • bRemaining 12% was normal adrenal (6%) and fat (6%).

  • cRemaining 9% was skeletal muscle.

  • dRemaining 15% was skeletal muscle.

  • eP values by Relative Expression Analysis Tool (REST) analysis: Pt 007 VEGF: P < 0.001; Pt 031 VEGF: P = 0.001; Pt 035 VEGF: P < 0.001;KSP: P = 0.015.