First-in-human phase 1 study of MK-1248, an anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR) monoclonal antibody, as monotherapy or in combination with pembrolizumab in patients with advanced solid tumors.
2018; Lippincott Williams & Wilkins; Volume: 36; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2018.36.15_suppl.3029
ISSN1527-7755
AutoresRavit Geva, Mark Voskoboynik, Amy M. Beebe, Jennifer Gwo, Konstantin Dobrenkov, Elliot Chartash, Georgina V. Long,
Tópico(s)Immunotherapy and Immune Responses
Resumo3029 Background: MK-1248 is a humanized IgG4 agonist monoclonal antibody (mAb) that targets GITR. GITR is expressed on regulatory T cells (Treg), resting CD4+ and CD8+ T cells, NK (natural killer) cells and NK T cells. Ligation of GITR decreases Treg-mediated suppression and enhances T cell proliferation, effector functions, and survival. Methods: MK-1248 was tested alone or in combination with pembrolizumab at a starting dose of 0.12 mg in both arms. Pembrolizumab dose was fixed at 200 mg. Both study drugs were administered intravenously every 3 weeks. Total number of intended doses of MK-1248 and pembrolizumab was 4 and 35, respectively. The study objective was to determine safety and tolerability, maximum tolerated dose (MTD), pharmacokinetic (PK), and pharmacodynamic (PD) profiles of MK-1248 as a monotherapy and in combination with pembrolizumab. Results: Data were available from 37 pts: 20 pts treated with MK-1248 monotherapy and 17 pts treated with MK-1248 + pembrolizumab combination therapy. Tumor types: colorectal cancer (8 pts), melanoma (5 pts), renal cell carcinoma (4 pts) and 20 pts with 16 other solid tumors. Maximum dose of MK-1248 tested: 170 mg (monotherapy) and 60 mg (combination). MK-1248 was well tolerated. Of the 37 pts treated, 36 pts (97.3%) had ≥1 adverse event (AE) and 17 pts (48.6%) had ≥1 treatment-related AE. Common AEs were: vomiting, anemia, decreased appetite, abdominal pain, cough, diarrhea, nausea, fatigue, headache and pyrexia. Infusion related reactions occurred in 6 (16.2%) pts. Eighteen pts had Grade 3-5 AEs (48.6%), 3 (8.1%) were treatment-related. Serious adverse events (SAE) occurred in 6 pts (30.0%) in monotherapy arm and 5 pts (29.4%) in combination arm. No DLT or treatment-related deaths were observed. One CR and 2 PR were observed in the study. Conclusions: MK-1248 at the dose up to 170 mg as monotherapy and 60 mg in combination with pembrolizumab was well tolerated with no dose limiting toxicities or treatment-related deaths. Responses were observed when MK-1248 was administered in combination with pembrolizumab. Clinical trial information: NCT02553499.
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