A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours.
BACKGROUND:PG545 (pixatimod) is a novel immunomodulatory agent, which has been demonstrated to stimulate innate immune responses against tumours in preclinical cancer models. METHODS:This Phase I study investigated the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of PG545 monotherapy. Escalating doses of PG545 were administered to patients with advanced solid malignancies as a weekly 1-h intravenous infusion. RESULTS:Twenty-three subjects were enrolled across four cohorts (25, 50, 100 and 150 mg). Three dose-limiting toxicities (DLTs)-hypertension (2), epistaxis (1)-occurred in the 150 mg cohort. No DLTs were noted in the 100 mg cohort, which was identified as the maximum-tolerated dose. No objective responses were reported. Best response was stable disease up to 24 weeks, with the disease control rate in evaluable subjects of 38%. Exposure was proportional up to 100 mg and mean half-life was 141 h. The pharmacodynamic data revealed increases in innate immune cell activation, plasma IFNγ, TNFα, IP-10 and MCP-1. CONCLUSION:PG545 demonstrated a tolerable safety profile, proportional PK, evidence of immune cell stimulation and disease control in some subjects. Taken together, these data support the proposed mechanism of action, which represents a promising approach for use in combination with existing therapies.
Dredge, K; Brennan, TV; Hammond, E; Lickliter, JD; Lin, L; Bampton, D; Handley, P; Lankesheer, F; Morrish, G; Yang, Y; Brown, MP; Millward, M
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