GSK and Merck, known as MSD outside the US and Canada, announced the initiation of a phase I clinical trial designed to evaluate GSK’s investigational immunotherapy GSK3174998 as monotherapy and in combination with Merck’s anti-PD-1 therapy, Keytruda (pembrolizumab) in patients with locally advanced, recurrent or metastatic solid tumour(s) that have progressed after standard treatment.

GSK3174998 is a humanised IgG1 anti-OX40 monoclonal antibody that was identified through a collaboration with MD Anderson Cancer Center. 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. GSK3174998 is one of a number of early stage assets in GSK’s oncology pipeline focused on fighting the fundamental drivers of cancer. 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.

Keytruda is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumour aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda. Keytruda is also indicated at the same dosing for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. These indications are approved under accelerated approval based on tumour response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for these indications may be contingent upon verification and description of clinical benefit in the confirmatory trials.

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.”

“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.”