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Dose escalation results from a first-in-human, phase 1 study of glucocorticoid-induced TNF receptor–related protein agonist AMG 228 in patients with advanced solid tumors

Overview of attention for article published in Journal for Immunotherapy of Cancer, September 2018
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (63rd percentile)

Mentioned by

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8 tweeters

Citations

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40 Dimensions

Readers on

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64 Mendeley
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Title
Dose escalation results from a first-in-human, phase 1 study of glucocorticoid-induced TNF receptor–related protein agonist AMG 228 in patients with advanced solid tumors
Published in
Journal for Immunotherapy of Cancer, September 2018
DOI 10.1186/s40425-018-0407-x
Pubmed ID
Authors

Ben Tran, Richard D. Carvajal, Aurelien Marabelle, Sandip Pravin Patel, Patricia M. LoRusso, Erik Rasmussen, Gloria Juan, Vijay V. Upreti, Courtney Beers, Gataree Ngarmchamnanrith, Patrick Schöffski

Abstract

This open-label, first-in-human, phase 1 study evaluated the safety, pharmacokinetics, pharmacodynamics, and maximum tolerated dose (MTD) of AMG 228, an agonistic human IgG1 monoclonal antibody targeting glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), in patients with refractory advanced solid tumors. AMG 228 was administered intravenously every 3 weeks (Q3W). Dose escalation was in two stages: single-patient cohorts (3, 9, 30, and 90 mg), followed by "rolling six" design (n = 2-6; 180, 360, 600, 900, and 1200 mg). Primary endpoints included incidence of dose-limiting toxicities (DLTs), AEs, and pharmacokinetics. Additional endpoints were objective response and pharmacodynamic response. Thirty patients received AMG 228, which was well tolerated up to the maximum planned dose (1200 mg). No DLTs occurred; the MTD was not reached. The most common treatment-related AEs were fatigue (13%), infusion-related reaction (7%), pyrexia (7%), decreased appetite (7%), and hypophosphatemia (7%). Two patients had binding anti-AMG 228 antibodies (one at baseline); no neutralizing antibodies were detected. AMG 228 exhibited target-mediated drug disposition, and serum exposure was approximately dose proportional at 180-1200 mg and greater than dose proportional at 3-1200 mg. Doses > 360 mg Q3W achieved serum trough coverage for 95% in vitro GITR occupancy. Despite GITR coverage in peripheral blood and tumor biopsies, there was no evidence of T-cell activation or anti-tumor activity. In patients with advanced solid tumors, AMG 228 Q3W was tolerable up to the highest tested dose (1200 mg), exhibited favorable pharmacokinetics, and provided target coverage indicating a pharmacokinetic profile appropriate for longer intervals. However, there was no evidence of T-cell activation or anti-tumor activity with AMG 228 monotherapy. ClinicalTrials.gov, NCT02437916 .

Twitter Demographics

The data shown below were collected from the profiles of 8 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 64 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 64 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 17 27%
Student > Master 9 14%
Student > Bachelor 6 9%
Other 5 8%
Lecturer 3 5%
Other 6 9%
Unknown 18 28%
Readers by discipline Count As %
Medicine and Dentistry 14 22%
Immunology and Microbiology 11 17%
Biochemistry, Genetics and Molecular Biology 6 9%
Agricultural and Biological Sciences 5 8%
Pharmacology, Toxicology and Pharmaceutical Science 4 6%
Other 5 8%
Unknown 19 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 October 2018.
All research outputs
#3,796,122
of 13,644,952 outputs
Outputs from Journal for Immunotherapy of Cancer
#443
of 831 outputs
Outputs of similar age
#95,309
of 265,593 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#1
of 2 outputs
Altmetric has tracked 13,644,952 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 831 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 17.4. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 265,593 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.
We're also able to compare this research output to 2 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them