PMID- 21900113
OWN - NLM
STAT- MEDLINE
DCOM- 20120117
LR  - 20220414
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 29
IP  - 28
DP  - 2011 Oct 1
TI  - Phase I pharmacokinetic and pharmacodynamic dose-escalation study of RG7160 
      (GA201), the first glycoengineered monoclonal antibody against the epidermal 
      growth factor receptor, in patients with advanced solid tumors.
PG  - 3783-90
LID - 10.1200/JCO.2011.34.8888 [doi]
AB  - PURPOSE: We conducted a phase I dose-escalation study to characterize the safety, 
      efficacy, pharmacokinetic (PK), and pharmacodynamic properties of RG7160 (GA201), 
      a humanized and glycoengineered immunoglobulin G(1) anti-epidermal growth factor 
      receptor (EGFR) monoclonal antibody with enhanced antibody-dependent 
      cell-mediated cytotoxicity. PATIENTS AND METHODS: Seventy-five patients with 
      advanced EGFR-positive solid tumors received RG7160 (50 to 1,400 mg) administered 
      every week, every 2 weeks, or every 3 weeks. Dose escalation followed a 
      three-plus-three trial design. RESULTS: No maximum-tolerated dose was reached for 
      any dosing schedule. Common adverse events (AEs) included rash (80% of patients), 
      infusion-related reactions (77%), and hypomagnesemia (56%). Grades 3 and 4 AEs 
      were rash (grade 3, 25%), infusion-related reaction (grade 3, 7%; grade 4, 1%), 
      paronychia (grade 3, 3%), and hypomagnesemia (grade 3, 1%; grade 4, 1%). RG7160 
      exposure increased greater than proportionally over the 50- to 400-mg dose range 
      (with greater than proportional decline in clearance) and approximately dose 
      proportionally above 400 mg (where clearance plateaued). A marked reduction in 
      circulating natural killer cells and increased infiltration of immune effector 
      cells into skin rash were seen. Clinical efficacy included one complete response 
      and two partial responses in patients with colorectal cancer (including one with 
      KRAS mutation) and disease stabilization in 27 patients. CONCLUSION: RG7160 had 
      an acceptable safety profile with manageable AEs and demonstrated promising 
      efficacy in this heavily pretreated patient cohort. On the basis of modeling of 
      available PK parameters, the RG7160 dose selected for part two of this study is 
      1,400 mg on days 1 and 8 followed by 1,400 mg every 2 weeks.
FAU - Paz-Ares, Luis G
AU  - Paz-Ares LG
AD  - Instituto de Biomedicina de Sevilla and Hospital Universitario Virgen del Rocio, 
      Seville, Spain.
FAU - Gomez-Roca, Carlos
AU  - Gomez-Roca C
FAU - Delord, Jean-Pierre
AU  - Delord JP
FAU - Cervantes, Andres
AU  - Cervantes A
FAU - Markman, Ben
AU  - Markman B
FAU - Corral, Jesus
AU  - Corral J
FAU - Soria, Jean-Charles
AU  - Soria JC
FAU - Berge, Yann
AU  - Berge Y
FAU - Roda, Desamparados
AU  - Roda D
FAU - Russell-Yarde, Fiona
AU  - Russell-Yarde F
FAU - Hollingsworth, Simon
AU  - Hollingsworth S
FAU - Baselga, Jose
AU  - Baselga J
FAU - Umana, Pablo
AU  - Umana P
FAU - Manenti, Luigi
AU  - Manenti L
FAU - Tabernero, Josep
AU  - Tabernero J
LA  - eng
SI  - ClinicalTrials.gov/NCT00721266
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20110906
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Glycoproteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - V77J4WJF9Z (imgatuzumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse 
      effects/immunology/*pharmacokinetics
MH  - Antineoplastic Agents/*administration & dosage/*pharmacokinetics
MH  - Cohort Studies
MH  - Dose-Response Relationship, Drug
MH  - ErbB Receptors/antagonists & inhibitors/immunology
MH  - Female
MH  - Glycoproteins/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/*metabolism
MH  - Young Adult
EDAT- 2011/09/09 06:00
MHDA- 2012/01/18 06:00
CRDT- 2011/09/09 06:00
PHST- 2011/09/09 06:00 [entrez]
PHST- 2011/09/09 06:00 [pubmed]
PHST- 2012/01/18 06:00 [medline]
AID - JCO.2011.34.8888 [pii]
AID - 10.1200/JCO.2011.34.8888 [doi]
PST - ppublish
SO  - J Clin Oncol. 2011 Oct 1;29(28):3783-90. doi: 10.1200/JCO.2011.34.8888. Epub 2011 
      Sep 6.