PMID- 20068101
OWN - NLM
STAT- MEDLINE
DCOM- 20100412
LR  - 20201219
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 16
IP  - 2
DP  - 2010 Jan 15
TI  - Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human 
      hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in-human 
      study of patients with advanced solid tumors.
PG  - 699-710
LID - 10.1158/1078-0432.CCR-09-1365 [doi]
AB  - PURPOSE: The aims were to assess the safety, pharmacokinetics, maximum tolerated 
      dose, and antitumor activity of AMG 102, a fully human hepatocyte growth 
      factor/scatter factor (HGF/SF)-neutralizing monoclonal antibody, in patients with 
      solid tumors. EXPERIMENTAL DESIGN: Patients (N = 40) with refractory advanced 
      solid tumors were enrolled into six sequential dose-escalation cohorts (0.5, 1, 
      3, 5, 10, or 20 mg/kg AMG 102 i.v. every 2 weeks) and a dose-expansion cohort (20 
      mg/kg AMG 102 every 2 weeks). Safety, anti-AMG 102 antibody formation, 
      pharmacokinetics, tumor response, and exploratory biomarkers were assessed. 
      RESULTS: AMG 102 was well tolerated up to the planned maximum dose of 20 mg/kg, 
      and the maximum tolerated dose was not reached. Treatment-related adverse events 
      were generally mild and included fatigue (13%), constipation (8%), nausea (8%), 
      vomiting (5%), anorexia (5%), myalgia (5%), and hypertension (5%). Two patients 
      experienced dose-limiting toxicities: one patient (0.5 mg/kg cohort) experienced 
      grade 3 hypoxia and grade 3 dyspnea and one patient (1 mg/kg cohort) experienced 
      grade 3 upper gastrointestinal hemorrhage. No anti-AMG 102 antibodies were 
      detected, and AMG 102 had linear pharmacokinetics within the dose range 
      investigated. Sixteen of 23 (70%) evaluable patients had a best response of 
      stable disease with progression-free survival ranging from 7.9 to 40 weeks. 
      Circulating levels of the biomarker HGF/SF (bound and unbound) increased in a 
      dose-dependent manner, whereas soluble c-Met concentrations were generally 
      similar across doses. CONCLUSIONS: AMG 102 is safe and well tolerated, has a 
      favorable pharmacokinetic profile, and will be further investigated as a 
      monotherapy and in combination with other agents.
FAU - Gordon, Michael S
AU  - Gordon MS
AD  - Premiere Oncology of Arizona, Scottsdale, Arizona 85258, USA. 
      mgordon@premiereoncology.com
FAU - Sweeney, Christopher S
AU  - Sweeney CS
FAU - Mendelson, David S
AU  - Mendelson DS
FAU - Eckhardt, S Gail
AU  - Eckhardt SG
FAU - Anderson, Abraham
AU  - Anderson A
FAU - Beaupre, Darrin M
AU  - Beaupre DM
FAU - Branstetter, Daniel
AU  - Branstetter D
FAU - Burgess, Teresa L
AU  - Burgess TL
FAU - Coxon, Angela
AU  - Coxon A
FAU - Deng, Hongjie
AU  - Deng H
FAU - Kaplan-Lefko, Paula
AU  - Kaplan-Lefko P
FAU - Leitch, Ian M
AU  - Leitch IM
FAU - Oliner, Kelly S
AU  - Oliner KS
FAU - Yan, Lucy
AU  - Yan L
FAU - Zhu, Min
AU  - Zhu M
FAU - Gore, Lia
AU  - Gore L
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20100112
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 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 51WEW898IJ (rilotumumab)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Antibodies, Monoclonal/*administration & dosage/*adverse 
      effects/*pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/administration & dosage/adverse effects/pharmacokinetics
MH  - Disease Progression
MH  - Dose-Response Relationship, Drug
MH  - Drug Resistance, Neoplasm/drug effects
MH  - Female
MH  - Hepatocyte Growth Factor/immunology
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Mice
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
MH  - Young Adult
EDAT- 2010/01/14 06:00
MHDA- 2010/04/13 06:00
CRDT- 2010/01/14 06:00
PHST- 2010/01/14 06:00 [entrez]
PHST- 2010/01/14 06:00 [pubmed]
PHST- 2010/04/13 06:00 [medline]
AID - 1078-0432.CCR-09-1365 [pii]
AID - 10.1158/1078-0432.CCR-09-1365 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2010 Jan 15;16(2):699-710. doi: 10.1158/1078-0432.CCR-09-1365. 
      Epub 2010 Jan 12.