GSK3174998 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors (ENGAGE-1)

Summary

This is a first time in human (FTIH), open-label, non-randomized, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary clinical activity of GSK3174998 administered intravenously to participants with selected advanced or recurrent solid tumors. This dose-escalation study will assess the safety, activity of GSK3174998 as monotherapy (Part 1), in combination with pembrolizumab (Part 2), and potentially in combination with additional therapies. The study will be conducted in 2 parts, each part consisting of starting with a dose-escalation phase followed by a cohort expansion phase. GSK3174998 will first be evaluated as monotherapy in escalating doses. Once a dose of GSK3174998 has been identified that is both tolerable and demonstrates pharmacodynamic activity, enrollment of Part 2 may begin. In Part 2, escalating doses of GSK3174998 will be evaluated with fixed doses of pembrolizumab. The maximum duration of treatment with GSK3174998 and pembrolizumab will be approximately 2 years or 35 cycles, whichever comes first. The follow-up period for safety assessments will be a minimum of 3 months from the date of the last dose. The post-treatment follow-up period will include disease assessments every 12 weeks until documented progressive disease (PD). Approximately 141 participants with selected advanced or recurrent solid tumors will be enrolled.

Timeline

Start

2015-09-11

Primary completion

2020-04-29

Completion

2020-04-29

Publications

• Postel-Vinay S, Lam VK, Ros W, Bauer TM, Hansen AR, Cho DC, Stephen Hodi F, Schellens JHM, Litton JK, Aspeslagh S, Autio KA, Opdam FL, McKean M, Somaiah N, Champiat S, Altan M, Spreafico A, Rahma O, Paul EM, Ahlers CM, Zhou H, Struemper H, Gorman SA, Watmuff M, Yablonski KM, Yanamandra N, Chisamore MJ, Schmidt EV, Hoos A, Marabelle A, Weber JS, Heymach JV. First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1). J Immunother Cancer. 2023 Mar;11(3):e005301. doi: 10.1136/jitc-2022-005301.

Drugs

Indications