Evidence map›Paper›PMID 27422720›Full record

ArticleInvestigational new drugs2016

A phase I dose-escalation study of LY2875358, a bivalent MET antibody, given as monotherapy or in combination with erlotinib or gefitinib in Japanese patients with advanced malignancies.

Kiyotaka Yoh, Toshihiko Doi, Hironobu Ohmatsu, Takashi Kojima, Hideaki Takahashi, Yoshitaka Zenke, Volker Wacheck, Sotaro Enatsu, Takashi Nakamura, Kellie Turner and 1 more

Open access · hybridAbstract readClinical Trial, Phase I
In one paragraph

Article in Investigational new drugs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 13 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Kiyotaka YohNational Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa, Chiba, 277-8577, Japan.
Toshihiko DoiNational Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa, Chiba, 277-8577, Japan. tdoi@east.ncc.go.jp.ORCID 0000-0003-2042-6829
Hironobu OhmatsuNational Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa, Chiba, 277-8577, Japan.
Takashi KojimaNational Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa, Chiba, 277-8577, Japan.
Hideaki TakahashiNational Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa, Chiba, 277-8577, Japan.
Yoshitaka ZenkeNational Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa, Chiba, 277-8577, Japan.
Volker WacheckEli Lilly and Company, Indianapolis, IN, USA.
Sotaro EnatsuEli Lilly Japan K. K., Kobe, Japan.
Takashi NakamuraEli Lilly Japan K. K., Kobe, Japan.
Kellie TurnerEli Lilly and Company, Indianapolis, IN, USA.
Kazunori UenakaEli Lilly Japan K. K., Kobe, Japan.
National Cancer Center Hospital East · JPEli Lilly (Japan) · JPEli Lilly (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background MET is a tyrosine kinase receptor involved in the regulation of cell proliferation and migration. Reported here are the phase I dose-escalation results for LY2875358, a monoclonal antibody against MET, in Japanese patients with advanced malignancies. Methods The study comprised a 3 + 3 dose-escalation part for LY2875358 monotherapy in patients with advanced malignancies (Part A) followed by an assessment of LY2875358 in combination with erlotinib or gefitinib in patients with non-small cell lung cancer (Part B). LY2875358 was administered once every 2 weeks. The primary objective was to evaluate the safety and tolerability of LY2875358; secondary objectives included evaluation of pharmacokinetics, pharmacodynamics, and antitumor activity. Results Eleven patients received LY2875358 monotherapy at 3 dose levels (700 mg, N = 3; 1400 mg, N = 3; 2000 mg, N = 5) and 6 patients received LY2875358 2000 mg in combination with erlotinib (N = 3) or gefitinib (N = 3). No dose-limiting toxicities or serious adverse events related to LY2875358 were observed. The most frequently reported drug-related adverse events were hypoalbuminemia (2 patients) in Part A and dermatitis acneiform (4 patients) in Part B. LY2875358 area under the curve (AUC) and maximum concentration (Cmax) increased with dose over the dose range of 700 mg to 2000 mg. A best response of stable disease was achieved by 2/11 patients in Part A and 4/6 patients in Part B (disease control rate: 35 %). Conclusions LY2875358 at doses up to 2000 mg demonstrated a favorable safety and tolerability profile as monotherapy or in combination with erlotinib or gefitinib in Japanese patients with advanced malignancies.

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic AgentsErlotinib HydrochlorideQuinazolinesAdultAgedAntineoplastic Combined Chemotherapy ProtocolsAsian PeopleFemaleGefitinibHumansMaleMiddle AgedNeoplasmsProto-Oncogene Proteins c-metTreatment OutcomeAntibodies, Monoclonal, HumanizedAntineoplastic AgentsemibetuzumabErlotinib HydrochlorideGefitinibMET protein, humanProto-Oncogene Proteins c-metQuinazolinesAntibodies, monoclonalEpidermal growth factor receptorLY2875358METPharmacokineticsSolid tumors

Identifiers

PMID27422720
PMCPMC5007274
OpenAlexW2463490825

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.