Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies
Posted on 2019-08-23 - 04:25
Abstract 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.
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Naing, Aung; Infante, Jeffrey; Goel, Sanjay; Burris, Howard; Black, Chelsea; Marshall, Shannon; et al. (2019). Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4641260.v1
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AUTHORS (21)
AN
Aung Naing
JI
Jeffrey Infante
SG
Sanjay Goel
HB
Howard Burris
CB
Chelsea Black
SM
Shannon Marshall
IA
Ikbel Achour
SB
Susannah Barbee
RM
Rena May
CM
Chris Morehouse
KP
Kristen Pollizzi
XS
Xuyang Song
KS
Keith Steele
NE
Nairouz Elgeioushi
FW
Farzana Walcott
JK
Joyson Karakunnel
PL
Patricia LoRusso
AW
Amy Weise
JE
Joseph Eder
BC
Brendan Curti