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https://hdl.handle.net/2440/114176
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Type: | Journal article |
Title: | A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours |
Author: | Dredge, K. Brennan, T. Hammond, E. Lickliter, J. Lin, L. Bampton, D. Handley, P. Lankesheer, F. Morrish, G. Yang, Y. Brown, M. Millward, M. |
Citation: | British Journal of Cancer, 2018; 118(8):1035-1041 |
Publisher: | Nature Publishing Group |
Issue Date: | 2018 |
ISSN: | 0007-0920 1532-1827 |
Statement of Responsibility: | 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 and Michael Millward |
Abstract: | 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. |
Keywords: | Cancer immunotherapy; drug development |
Rights: | © Cancer Research UK 2018 |
DOI: | 10.1038/s41416-018-0006-0 |
Published version: | http://dx.doi.org/10.1038/s41416-018-0006-0 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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