Merck presents early data for STING agonist in advanced solid tumors/lymphomas
Merck announced the first presentation of preliminary data from a Phase 1 clinical trial evaluating MK-1454, an investigational STING agonist, as monotherapy and in combination with Keytruda, Merck's anti-PD-1 therapy, in patients with advanced solid tumors or lymphomas. MK-1454 is one of more than 20 novel investigational immuno-therapeutic candidates Merck is evaluating as part of its broad oncology pipeline. In this Phase 1, open-label, multi-arm, multicenter, dose-escalation clinical trial, MK-1454 was administered to patients with advanced solid tumors or lymphomas by intratumoral injection every week for nine weeks for three cycles then every three weeks thereafter. Dose escalations for MK-1454 were 10-3,000 microg and 90-2,000 microg using accelerated titration followed by modified toxicity probability interval design. Keytruda was administered as an intravenous 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 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% of patients, with median reductions of 83% in the size of both target-injected and non-injected tumors. 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% and 48% for the monotherapy and combination arms, respectively. Treatment-related adverse events occurred in 82.6% and 82.1% of patients in monotherapy and combination arms, respectively. TRAEs resulting in trial discontinuation occurred in 7.1% of patients in the combination arm. No TRAE discontinuations were recorded in patients in the monotherapy arm.