MSD announces the first presentation of preliminary data from a Phase 1 clinical trial evaluating MK-1454, an investigational STING agonist for cancer treatment.
MSD are evaluating MK-1454, an investigational STING agonist for cancer monotherapy and in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with advanced solid tumours or lymphomas.
MK-1454 is one of more than 20 novel investigational immuno-therapeutic candidates MSD is evaluating as part of its broad oncology pipeline. The findings for MK-1454 were accepted as a late-breaking abstract and are being presented today in a poster discussion session at the ESMO 2018 Congress (Abstract #LBA15).
In this Phase 1, open-label, multi-arm, multicenter, dose-escalation clinical trial (NCT03010176), MK-1454 was administered to patients with advanced solid tumours or lymphomas by intratumoral injection every week for nine weeks for three cycles then every three weeks thereafter. KEYTRUDA was administered as an intravenous (IV) injection at a dose of 200 mg every three weeks. Patients receiving MK-1454 as monotherapy who progressed while on therapy were eligible for crossover to the MK-1454-KEYTRUDA combination arm. Study objectives oncology included evaluation of safety, tolerability, pharmacodynamics, pharmacokinetics and tumor responses evaluated using RECIST v1.1 criteria.
Interim data presented at ESMO were based on findings from 26 patients enrolled in the MK-1454 monotherapy arm and 25 patients enrolled in the combination arm with KEYTRUDA, plus 9 patients who crossed over from monotherapy to receive the combination regimen. In the monotherapy arm, no complete or partial responses were observed. In the combination arm, partial responses were observed in 24 percent of patients, with median reductions of 83 percent in the size of both target-injected and non-injected tumours. At the time of analysis, all of the partial responses were ongoing and had lasted six months or longer. None of the responders had previously received a PD-1/PD-L1 inhibitor therapy. The disease control rates were 20 percent and 48 percent for the monotherapy and combination arms, respectively.
Treatment-related adverse events (TRAEs) occurred in 82.6 percent (n=19/23) and 82.1 percent (n=23/28) of patients in monotherapy and combination arms, respectively.
STING is a signalling molecule that plays an important role in the body’s first line of defence against pathogens, such as bacteria and viruses (innate immune system). When activated, STING triggers the production of inflammatory proteins that can stimulate the immune system leading to the deployment of T cells, which are important in generating an effective immune mediated response to cancer cells.
MSD is exploring the investigational STING agonist for cancer treatment by looking at the role of the STING pathway across a variety of tumours as monotherapy and in combination with the company’s anti-PD-1 therapy, KEYTRUDA. MK-1454 is an investigational small molecule STING agonist administered as an intratumoral injection that is currently being evaluated in a Phase 1 clinical trial for the treatment of solid tumors and lymphomas.
KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumour cells. KEYTRUDA is a humanised monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
MSD has the industry’s largest immuno-oncology clinical research program. There are currently more than 850 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. These include the KEYNOTE-048 trial which met primary end points, and an NSCLC trial where Bemcentinib in combination with KEYTRUDA met primary end points.
Dr. Eric H. Rubin, senior vice president, early-stage development, clinical oncology, Merck Research Laboratories said, “Merck is advancing a broad pipeline focused on the development of novel therapies with potential to provide meaningful clinical benefit to people with advanced cancers. We are encouraged by these early findings with our STING agonist for cancer treatment, most notably the observations of several robust anti-tumour responses in patients receiving MK-1454 in combination with KEYTRUDA. Further studies are ongoing.”