511TiPA phase I, open-label study of GSK1795091 administered in combination with immunotherapies in participants with advanced solid tumours (NCT03447314)

AbstractBackgroundToll-like receptor (TLR) activation can enhance a range of antitumor immune responses via production of inflammatory cytokines and modulation of immune cells in the tumor microenvironment. GSK1795091 is a synthetic TLR4 agonist that showed immunomodulatory activity in preclinical cancer models (Gao et al. J Clin Oncol 2018) and successfully completed a safety, pharmacokinetic (PK) and pharmacodynamic (PD) study using IV administration in healthy volunteers. The current study will evaluate GSK1795091 with immunotherapies that have highly complementary mechanisms of action and supporting preclinical data (e.g. GSK3174998 [an OX40 agonist], GSK3359609 [an ICOS agonist], or pembrolizumab [a PD-1 inhibitor]) with the aim of generating greater antitumor activity than with monotherapy.Trial designThis is a Phase I, open-label, non-randomized study in patients ( ≥18 years) with advanced solid tumors who have progressed on, or are ineligible for, standard therapy. In Part 1, up to 72 patients will be divided into 3 arms: GSK1795091 (50–250 ng IV; dose escalation) plus either GSK3174998 (24 mg IV), GSK3359609 (80 mg IV), or pembrolizumab (200 mg I V). GSK1795091 will be given weekly for 12 weeks; combination partners will be administered every 3 weeks (q3w) from Week 3 to allow a 2-week GSK1795091 monotherapy run-in period. After Week 12, GSK1795091 will be administered q3w, coinciding with the combination partner. Up to 6 participants per do se level may ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research