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MK-1248 + pembrolizumab is an investigational intravenous combination therapy comprised of **MK-1248**, a humanized immunoglobulin G4 anti-GITR monoclonal antibody agonist, and **pembrolizumab** (Keytruda), an anti–PD-1 monoclonal antibody. MK-1248 targets the **glucocorticoid-induced tumor necrosis factor receptor (GITR)**, which, when activated, decreases regulatory T cell–mediated suppression and enhances proliferation, effector functions, and survival of T cells. Pembrolizumab inhibits the **programmed cell death protein 1 (PD-1)** checkpoint, thereby enhancing T cell–mediated antitumor immunity. Developed and tested by Merck Sharp & Dohme Corp. (Merck), this drug combination has been evaluated in **advanced solid tumors**, with primary endpoints focusing on safety, tolerability, and identification of maximum tolerated dose[1][3][5]. Exploratory endpoints included antitumor activity, immune biomarker modulation, and pharmacokinetics/pharmacodynamics[2][3][5]. In phase 1 trials (NCT02553499), responses were seen only in the combination arm (one complete response, two partial responses) with an objective response rate of 18% (combination) and a disease control rate of 41% (combination)[4][5].
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