First Time in Humans (FTIH) Study of GSK3368715 in Participants With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL)

Study 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.

Primary Outcome

A DLT is considered by the investigator to be clinically relevant,attributed event during the first 21days of intervention meeting the following criteria:Non-hematologic toxicity:Aspartate Aminotransferase(AST)/Alanine Aminotransferase(ALT) Grade 3/4,ALT\>=5 times Upper limit of Normal(ULN),ALT\>=3times ULN(\>=4 weeks),ALT\>=3 times ULN plus(+)bilirubin\>=2 times ULN,ALT \>= 3 times ULN+liver symptoms or International Normalization Ratio(INR)\>1.5.Nausea:Grade 3;Vomiting or diarrhea:Grade3/4(\>3

Interventions

• DRUG GSK3368715