First Time in Humans (FTIH) Study of GSK3368715 in Participants With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL)
Status:
Completed
Trial end date:
2021-03-04
Target enrollment:
Participant gender:
Summary
Arginine methylation mediated by protein arginine methyl-transferases (PRMTs) is an important
post-translational modification of proteins involved in a diverse range of cellular
processes. Misregulation and overexpression of PRMT1 (a type I PRMT) has been associated with
a number of solid and hematopoietic cancers. GSK3368715 leads to inhibition of tumor cell
growth across tumor types with cytotoxic response observed in lymphoma, acute myeloid
leukemia (AML) and a subset of solid tumor cell lines. This study will assess the safety,
pharmacokinetics (PK), pharmacodynamics (PD), food effect and preliminary clinical activity
of GSK33368715 in participants with relapsed/refractory DLBCL and selected solid tumors with
frequent methyl-thioadenosine phosphorylase (MTAP)-deficiency. The study will consist of two
parts. In Part 1 (Dose Escalation) escalating doses of GSK3368715 will be evaluated and
recommended phase 2 dose (RP2D) will be established in participants with selected solid
relapsed/refractory tumors. Once a RP2D is identified, a food effect sub-study will be
initiated to determine the effect of a high-fat, high calorie meal on the bioavailability of
GSK3368715. In Part 2 (Dose Expansion), this RP2D will be further investigated in two
expansion cohorts; participants with DLBCL (Expansion Cohort 2A) and relapsed/refractory
solid tumors including pancreatic, bladder, and non-small cell lung cancer (NSCLC)(Expansion
Cohort 2B). The study includes a screening period, an intervention period and follow up.