Figure 5.

Biological effects of motolimod in humans. The in vivo cytokine response to motolimod was assessed in women with advanced ovarian cancer who were treated with 40 mg/m² of PLD in combination with motolimod at 2.5 (n=3), 3.0 (n=3), or 3.5 mg/m² (n=7). Plasma was collected prior to the initial dose of motolimod and 8 hours post-dose, and levels of selected cytokines and chemokines were assessed using the HumanMAP^® panel. (A) Immune mediator concentrations were log (base 2) transformed, and fold changes were calculated for each analyte level by dividing the post-dose value by the corresponding value from the pre-dose sample. The corresponding heat map for mediators exhibiting a mean log fold increase of ≥ 1.3 over baseline is shown. (B) Mediators that broadly demonstrated a dose-related increase of ≥ 1.3-fold at 1 or more of the motolimod dose levels included G-CSF, IL-6, MIP-1β, and MCP-1, and this response was maintained over two treatment cycles. (C) To demonstrate the translational relevance of the anti-tumor response seen in NSG-HIS mice treated with the combination of PLD + motolimod, the murine plasma mediator response was compared to that observed in clinical participants. Many of the mediators induced in the plasma of women with ovarian cancer (n=13) were also induced in NSG-HIS mice (n=6) following motolimod administration. Overall, the magnitude of the mediator response (fold increase with respect to baseline/control) in mice dosed with 15 mg/m² motolimod was comparable to what was seen in ovarian subjects at the 3.5 mg/m² dose.

Response following PLD + motolimod in recurrent stage 3c ovarian cancer. (D) This subject with recurrent non-target (non-measurable) disease was enrolled on study GOG-9925 and received PLD 40 mg/m² (day 1), followed by 2.5 mg/m² of motolimod (days 3, 10, and 17) for 2 cycles without major incident. Her disease remained stable during a 5-month treatment-free interval necessitated by a shortage in the global supply of PLD. Thereafter she received 4 additional cycles of PLD plus motolimod and achieved a complete response (no evidence of disease). (E) Swim plot illustrating the course of the 13 subjects who received the PLD plus motolimod combination.