J Immunother Cancer
BACKGROUND: The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies.
METHODS: MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics.
RESULTS: Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts.
CONCLUSIONS: MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration.
TRIAL REGISTRATION: NCT02013804 ; date of registration December 12, 2013.
Earle A. Chiles Research Institute
Naing, Aung; Infante, Jeffrey; Goel, Sanjay; Burris, Howard; Black, Chelsea; Marshall, Shannon; Achour, Ikbel; Barbee, Susannah; May, Rena; Morehouse, Chris; Pollizzi, Kristen; Song, Xuyang; Steele, Keith; Elgeioushi, Nairouz; Walcott, Farzana; Karakunnel, Joyson; LoRusso, Patricia; Weise, Amy; Eder, Joseph; Curti, Brendan; and Oberst, Michael, "Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies." (2019). Articles, Abstracts, and Reports. 1973.