- Title
- A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours
- Creator
- Dredge, Keith; Brennan, Todd V.; Millward, Michael; Hammond, Edward; Lickliter, Jason D.; Liwen, Lin; Bampton, Darryn; Handley, Paul; Lankesheer, Fleur; Morrish, Glynn; Yang, Yiping
- Relation
- British Journal of Cancer Vol. 118, Issue 8, p. 1035-1041
- Publisher Link
- http://dx.doi.org/10.1038/s41416-018-0006-0
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2018
- Description
- 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.
- Subject
- cancer immunotherapy; drug development; tumors; pixatimod; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1458538
- Identifier
- uon:45453
- Identifier
- ISSN:0007-0920
- Language
- eng
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