NCT03666988

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

A Phase I, Open-label, Dose-escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK3368715 in Participants With Solid Tumors and DLBCL

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Neoplasms

Interventions

Type	Name	Description
DRUG	GSK3368715	GSK3368715 will be available with dosing strengths of 25 mg, 100 mg and 250 mg to be administered once daily as an oral capsule.
DRUG	GSK3368715	GSK3368715 will be available in Immediate release (IR) white film coated tablet with dosing strengths of 50 mg, 100 mg and 250 mg to be administered orally once daily .

Timeline

• Start date: 2018-10-22
• Primary completion: 2021-03-04
• Completion: 2021-03-04
• First posted: 2018-09-12
• Last updated: 2022-05-20
• Results posted: 2022-05-20

Locations

9 sites across 4 countries: United States, Australia, Canada, Spain

Regulatory

• FDA-regulated drug study