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Phase II evaluation of LY2603618, a first-generation CHK1 inhibitor, in combination with pemetrexed in patients with advanced or metastatic non-small cell lung cancer

Overview of attention for article published in Investigational New Drugs, June 2016
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Title
Phase II evaluation of LY2603618, a first-generation CHK1 inhibitor, in combination with pemetrexed in patients with advanced or metastatic non-small cell lung cancer
Published in
Investigational New Drugs, June 2016
DOI 10.1007/s10637-016-0368-1
Pubmed ID
Authors

Giorgio Scagliotti, Jin Hyoung Kang, David Smith, Richard Rosenberg, Keunchil Park, Sang-We Kim, Wu-Chou Su, Thomas E. Boyd, Donald A. Richards, Silvia Novello, Scott M. Hynes, Scott P. Myrand, Ji Lin, Emily Nash Smyth, Sameera Wijayawardana, Aimee Bence Lin, Mary Pinder-Schenck

Abstract

Introduction LY2603618 is a selective inhibitor of checkpoint kinase 1 (CHK1) protein kinase, a key regulator of the DNA damage checkpoint, and is predicted to enhance the effects of antimetabolites, such as pemetrexed. This phase II trial assessed the overall response rate, safety, and pharmacokinetics (PK) of LY2603618 and pemetrexed in patients with non-small cell lung cancer (NSCLC). Methods In this open-label, single-arm trial, patients with advanced or metastatic NSCLC progressing after a prior first-line treatment regimen (not containing pemetrexed) and Eastern Cooperative Oncology Group performance status ≤2 received pemetrexed (500 mg/m(2), day 1) and LY2603618 (150 mg/m(2), day 2) every 21 days until disease progression. Safety was assessed using Common Terminology Criteria for Adverse Events v3.0. Serial blood samples were collected for PK analysis after LY2603618 and pemetrexed administration. Expression of p53, as measured by immunohistochemistry and genetic variant analysis, was assessed as a predictive biomarker of response. Results Fifty-five patients were enrolled in the study. No patients experienced a complete response; a partial response was observed in 5 patients (9.1 %; 90 % CI, 3.7-18.2) and stable disease in 20 patients (36.4 %). The median progression-free survival was 2.3 months (range, 0-27.1). Safety and PK of LY2603618 in combination with pemetrexed were favorable. No association between p53 status and response was observed. Conclusions There was no significant clinical activity of LY2603618 and pemetrexed combination therapy in patients with advanced NSCLC. The results were comparable with historical pemetrexed single-agent data, with similar safety and PK profiles being observed.

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Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 5 16%
Other 5 16%
Student > Ph. D. Student 5 16%
Researcher 4 13%
Student > Bachelor 3 10%
Other 9 29%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 26%
Unspecified 8 26%
Agricultural and Biological Sciences 7 23%
Pharmacology, Toxicology and Pharmaceutical Science 4 13%
Chemistry 2 6%
Other 2 6%

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 December 2017.
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#9,823,555
of 12,299,992 outputs
Outputs from Investigational New Drugs
#497
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#195,655
of 268,628 outputs
Outputs of similar age from Investigational New Drugs
#5
of 6 outputs
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