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A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing…

Overview of attention for article published in BMC Cancer, September 2017
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Title
A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer
Published in
BMC Cancer, September 2017
DOI 10.1186/s12885-017-3641-6
Pubmed ID
Authors

Kerry Lynn Reynolds, Philippe L. Bedard, Se-Hoon Lee, Chia-Chi Lin, Josep Tabernero, Maria Alsina, Ezra Cohen, José Baselga, George Blumenschein, Donna M. Graham, Ignacio Garrido-Laguna, Dejan Juric, Sunil Sharma, Ravi Salgia, Abdelkader Seroutou, Xianbin Tian, Rose Fernandez, Alex Morozov, Qing Sheng, Thiruvamoor Ramkumar, Angela Zubel, Yung-Jue Bang

Abstract

Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. This open-label, dose-finding study comprised dose escalation, followed by expansion in patients with squamous cell carcinoma of the head and neck or esophagus, and HER2-overexpressing metastatic breast cancer or gastric cancer. During dose escalation, patients received LJM716 intravenous once weekly (QW) or every two weeks (Q2W), in 28-day cycles. An adaptive Bayesian logistic regression model was used to guide dose escalation and establish the RDE. Exploratory pharmacodynamic tumor studies evaluated modulation of HER3 signaling. Patients received LJM716 3-40 mg/kg QW and 20 mg/kg Q2W (54 patients; 36 patients at 40 mg/kg QW). No dose-limiting toxicities (DLTs) were reported during dose-escalation. One patient experienced two DLTs (diarrhea, hypokalemia [both grade 3]) in the expansion phase. The RDE was 40 mg/kg QW, providing drug levels above the preclinical minimum effective concentration. One patient with gastric cancer had an unconfirmed partial response; 17/54 patients had stable disease, two lasting >30 weeks. Down-modulation of phospho-HER3 was observed in paired tumor samples. LJM716 was well tolerated; the MTD was not reached, and the RDE was 40 mg/kg QW. Further development of LJM716 is ongoing. Clinicaltrials.gov registry number NCT01598077 (registered on 4 May, 2012).

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 65 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 65 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 20%
Other 7 11%
Student > Ph. D. Student 7 11%
Student > Bachelor 6 9%
Student > Master 5 8%
Other 14 22%
Unknown 13 20%
Readers by discipline Count As %
Medicine and Dentistry 19 29%
Pharmacology, Toxicology and Pharmaceutical Science 6 9%
Biochemistry, Genetics and Molecular Biology 5 8%
Nursing and Health Professions 4 6%
Economics, Econometrics and Finance 4 6%
Other 8 12%
Unknown 19 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 15 September 2017.
All research outputs
#18,572,036
of 23,002,898 outputs
Outputs from BMC Cancer
#5,460
of 8,356 outputs
Outputs of similar age
#242,465
of 316,004 outputs
Outputs of similar age from BMC Cancer
#83
of 119 outputs
Altmetric has tracked 23,002,898 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,356 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 21st percentile – i.e., 21% 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 316,004 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 119 others from the same source and published within six weeks on either side of this one. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.