Evidence map›Paper›PMID 26507836›Full record

ArticleTargeted oncology2016

Phase 1 Study of Monotherapy with KHK2866, an Anti-Heparin-Binding Epidermal Growth Factor-Like Growth Factor Monoclonal Antibody, in Patients with Advanced Cancer.

John Sarantopoulos, Monica M Mita, Michael J Birrer, Lee D Cranmer, Luis T Campos, Xiaoping Zhang, Penelope Bristow, Hidekuni Kaito, Vincent Strout, Luis H Camacho

Abstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

Article in Targeted oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
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

10 authors at 6 institutions in 1 country.

John SarantopoulosInstitute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio, 4th Floor, Zeller Building, 7979 Wurzbach Road, San Antonio, TX, 78229, USA. sarantopoulo@uthscsa.edu.
Monica M MitaSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Michael J BirrerGillette Center of Gynecologic Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Lee D CranmerUniversity of Arizona Cancer Center, Tuscon, AZ, USA.
Luis T CamposOncology Consultants, Houston, TX, USA.
Xiaoping ZhangKyowa Hakko Kirin Pharma, Inc., Princeton, NJ, USA.
Penelope BristowKyowa Hakko Kirin Pharma, Inc., Princeton, NJ, USA.
Hidekuni KaitoKyowa Hakko Kirin Pharma, Inc., Princeton, NJ, USA.
Vincent StroutKyowa Hakko Kirin Pharma, Inc., Princeton, NJ, USA.
Luis H CamachoOncology Consultants, Houston, TX, USA.
Kirin (United States) · USHematology Oncology Consultants · USCedars-Sinai Medical Center · USMassachusetts General Hospital · USThe University of Texas Health Science Center at San Antonio · USUniversity of Arizona Cancer Center

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Lei Zheng · 1991 to 2026
$59.1M
NCI NIH HHS P30 CA054174
6 · The paper itself

Abstract

backgroundKHK2866 is a recombinant, humanized, non-fucosylated, monoclonal antibody directed at heparin-binding epidermal growth factor-like growth factor (HB-EGF).

objectiveTo determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, potential immunogenicity, and preliminary clinical efficacy of KHK2866 monotherapy in patients with advanced and refractory cancer in a first-in-human, phase 1 study. MATERIALS AND

methodsUsing a standard 3 + 3 dose-escalation design, 20 patients received KHK2866 (0.3, 1, and 3 mg/kg) intravenously once weekly. Two additional patients received 0.1 mg/kg in a cohort which was subsequently added following protocol amendment.

resultsThe first three patients enrolled experienced grade 2 hypersensitivity (acute infusion reactions) after the first dose of KHK2866. After prophylactic treatment with an H1-blocker and corticosteroids in subsequently recruited patients, two grade 2 hypersensitivity reactions were observed in the remaining 19 patients. Grade 2/3 neurotoxicity appeared to be dose-limiting at 3 mg/kg in the original dose-escalation cohorts (n = 2), at 1 mg/kg in the MTD dose expansion cohort (n = 1), and at 0.1 mg/kg (n = 1). Neurotoxicity was manifested as complex partial seizure activity, aphasia, and confusion after first-dose administration. Pharmacokinetic exposure to KHK2866 increased proportionally to dose. Mean elimination half-life was 71.9-118 h over the dose range from 0.3 to 3 mg/kg. All KHK2866 doses decreased serum free HB-EGF levels, generally below the lower limit of quantification.

conclusionsThe study was terminated because of neuropsychiatric toxicity. The only predictive factor for neuropsychiatric toxicity was administration of KHK2866. These effects were reversible, but were not predictable. Their etiology is not presently understood. [Study registered at ClinicalTrials.gov #NCT0179291].

Indexed as

AdultAgedAntibodies, MonoclonalEGF Family of ProteinsFemaleHumansMaleMiddle AgedNeoplasmsAntibodies, MonoclonalEGF Family of Proteins

Identifiers

PMID26507836
OpenAlexW1850427692

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.