PMID- 27756788
OWN - NLM
STAT- MEDLINE
DCOM- 20170627
LR  - 20210105
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 23
IP  - 8
DP  - 2017 Apr 15
TI  - Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 
      Monoclonal Antibody.
PG  - 1929-1936
LID - 10.1158/1078-0432.CCR-16-1272 [doi]
AB  - Purpose: Urelumab is an agonist antibody to CD137 with potential application as 
      an immuno-oncology therapeutic. Data were analyzed to assess safety, 
      tolerability, and pharmacodynamic activity of urelumab, including the dose 
      selected for ongoing development in patients with advanced solid tumors and 
      lymphoma.Experimental Design: A total of 346 patients with advanced cancers who 
      had progressed after standard treatment received at least one dose of urelumab in 
      one of three dose-escalation, monotherapy studies. Urelumab was administered at 
      doses ranging from 0.1 to 15 mg/kg. Safety analyses included treatment-related 
      and serious adverse events (AEs), as well as treatment-related AEs leading to 
      discontinuation and death, with a focus on liver function test abnormalities and 
      hepatic AEs.Results: Urelumab doses between 1 and 15 mg/kg given every 3 weeks 
      resulted in a higher frequency of treatment-related AEs than 0.1 or 0.3 mg/kg 
      every 3 weeks. Dose was the single most important factor contributing to 
      transaminitis development, which was more frequent and severe at doses >/=1 mg/kg. 
      At the MTD of 0.1 mg/kg every 3 weeks, urelumab was relatively well tolerated, 
      with fatigue (16%) and nausea (13%) being the most common treatment-related AEs, 
      and was associated with immunologic and pharmacodynamic activity demonstrated by 
      the induction of IFN-inducible genes and cytokines.Conclusions: Integrated 
      evaluation of urelumab safety data showed significant transaminitis was strongly 
      associated with doses of >/=1 mg/kg. However, urelumab 0.1 mg/kg every 3 weeks was 
      demonstrated to be safe, with pharmacodynamic activity supporting continued 
      clinical evaluation of this dose as monotherapy and in combination with other 
      immuno-oncology agents. Clin Cancer Res; 23(8); 1929-36. (c)2016 AACR.
CI  - (c)2016 American Association for Cancer Research.
FAU - Segal, Neil H
AU  - Segal NH
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
FAU - Logan, Theodore F
AU  - Logan TF
AD  - Indiana University Simon Cancer Center, Indianapolis, Indiana.
FAU - Hodi, F Stephen
AU  - Hodi FS
AD  - Dana-Farber Cancer Institute, Boston, Massachusetts.
FAU - McDermott, David
AU  - McDermott D
AD  - Beth Israel Deaconess Medical Center, Boston, Massachusetts.
FAU - Melero, Ignacio
AU  - Melero I
AD  - Clinica Universidad de Navarra, Pamplona, Spain.
FAU - Hamid, Omid
AU  - Hamid O
AD  - The Angeles Clinic and Research Institute, Los Angeles, California.
FAU - Schmidt, Henrik
AU  - Schmidt H
AD  - Aarhus University Hospital, Aarhus, Denmark.
FAU - Robert, Caroline
AU  - Robert C
AD  - Gustave Roussy and Paris-Sud University Villejuif, Villejuif, France.
FAU - Chiarion-Sileni, Vanna
AU  - Chiarion-Sileni V
AD  - Istituto Oncologico Veneto, Padua, Italy.
FAU - Ascierto, Paolo A
AU  - Ascierto PA
AD  - Istituto Nazionale Tumori Fondazione "G. Pascale," Naples, Italy.
FAU - Maio, Michele
AU  - Maio M
AD  - University Hospital of Siena, Siena, Italy.
FAU - Urba, Walter J
AU  - Urba WJ
AD  - Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, 
      Oregon.
FAU - Gangadhar, Tara C
AU  - Gangadhar TC
AD  - Abramson Cancer Center of the University of Pennsylvania, Philadelphia, 
      Pennsylvania.
FAU - Suryawanshi, Satyendra
AU  - Suryawanshi S
AD  - Bristol-Myers Squibb, Princeton, New Jersey.
FAU - Neely, Jaclyn
AU  - Neely J
AD  - Bristol-Myers Squibb, Princeton, New Jersey.
FAU - Jure-Kunkel, Maria
AU  - Jure-Kunkel M
AD  - Bristol-Myers Squibb, Princeton, New Jersey.
FAU - Krishnan, Suba
AU  - Krishnan S
AD  - Bristol-Myers Squibb, Princeton, New Jersey.
FAU - Kohrt, Holbrook
AU  - Kohrt H
AD  - Stanford University School of Medicine, Stanford, California.
FAU - Sznol, Mario
AU  - Sznol M
AD  - Yale Comprehensive Cancer Center, New Haven, Connecticut.
FAU - Levy, Ronald
AU  - Levy R
AD  - Stanford University School of Medicine, Stanford, California. levy@stanford.edu.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20161018
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (4-1BB Ligand)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (TNFSF9 protein, human)
RN  - 230902QLLC (urelumab)
SB  - IM
MH  - 4-1BB Ligand/*agonists
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/administration & dosage/*adverse effects/pharmacokinetics
MH  - Antineoplastic Agents/administration & dosage/*adverse effects/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Melanoma/drug therapy
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
EDAT- 2016/11/01 06:00
MHDA- 2017/06/28 06:00
CRDT- 2016/11/01 06:00
PHST- 2016/05/19 00:00 [received]
PHST- 2016/08/10 00:00 [revised]
PHST- 2016/08/29 00:00 [accepted]
PHST- 2016/11/01 06:00 [pubmed]
PHST- 2017/06/28 06:00 [medline]
PHST- 2016/11/01 06:00 [entrez]
AID - 1078-0432.CCR-16-1272 [pii]
AID - 10.1158/1078-0432.CCR-16-1272 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2017 Apr 15;23(8):1929-1936. doi: 10.1158/1078-0432.CCR-16-1272. 
      Epub 2016 Oct 18.