GSK and Merck initiate Phase I trial of GSK3174998 with Keytruda

3 November 2015  •  Author: Victoria White

GSK and Merck have announced the initiation of a Phase I clinical trial designed to evaluate GSK’s GSK3174998 as monotherapy and in combination with Merck’s Keytruda (pembrolizumab) in patients with locally advanced, recurrent or metastatic solid tumours that have progressed after standard treatment.


“The initiation of this Phase I trial with GSK is an important step in identifying synergistic treatment combinations that can potentially enhance the activity we are seeing with Keytruda as a monotherapy,” said Dr Eric Rubin, vice president and therapeutic area head, oncology early stage development, Merck Research Laboratories. “We are looking forward to this trial progressing and to sharing the findings on the potential of the combination of Keytruda and GSK’s GSK3174998 in bringing forward improved outcomes for patients with advanced cancer.”

GSK3174998 and Keytruda use different aspects of the immune system

GSK3174998 is a humanised IgG1 anti-OX40 monoclonal antibody. OX40 is a tumour necrosis factor receptor expressed on the surface of activated CD4+ and CD8+ T cells. OX40 agonism results in stimulation of both immune effector and memory functions, while also attenuating the immunosuppressive regulatory T cells that are sometimes found in tumours. Keytruda is a humanised monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumour cells. Keytruda blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, and may affect both tumour cells and healthy cells.

Axel Hoos, Vice President Oncology R&D at GSK, said: “There have been meaningful advances in survival across several cancers recently, mostly based on single agent checkpoint modulatory drugs. The combination study of Keytruda with GSK’s OX40 agonist will seek to build on that progress with the aim of contributing further improvements for patients. We think combining these two agents that use different aspects of the immune system may be an important step toward achieving this goal.”

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