A Phase i study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours

Keith Dredge, Todd V. Brennan, Edward Hammond, Jason D. Lickliter, Liwen Lin, Darryn Bampton, Paul Handley, Fleur Lankesheer, Glynn Morrish, Yiping Yang, Michael P. Brown, Michael Millward

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47 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1035-1041
Number of pages7
JournalBritish Journal of Cancer
Issue number8
Publication statusPublished - 1 Apr 2018


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