A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours
Mené sur 23 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue les caractéristiques pharmacocinétiques et pharmacodynamiques, la dose maximale tolérée et l'activité antitumorale d'un composé appelé PG545 (pixatimod), un agent immunomodulateur dispensé en monothérapie par voie intraveineuse
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 enroled 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 IFN
γ, 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.