PMID- 24901237
OWN - NLM
STAT- MEDLINE
DCOM- 20141111
LR  - 20220309
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 111
IP  - 2
DP  - 2014 Jul 15
TI  - Phase I ficlatuzumab monotherapy or with erlotinib for refractory advanced solid 
      tumours and multiple myeloma.
PG  - 272-80
LID - 10.1038/bjc.2014.290 [doi]
AB  - BACKGROUND: Ficlatuzumab, a humanised hepatocyte growth factor (HGF) IgG1kappa 
      inhibitory monoclonal antibody, was evaluated for recommended phase II dose 
      (RP2D), safety, pharmacokinetics (PKs), antidrug antibody (ADA), pharmacodynamics 
      (PDs) and antitumour activity as monotherapy or combined with erlotinib. METHODS: 
      Patients with solid tumours received ficlatuzumab 2, 5, 10 or 20 mg kg(-1) 
      intravenously every 2 weeks (q2w). Additional patients were treated at the RP2D 
      erlotinib. RESULTS: Forty-one patients enrolled at doses ⩽20 mg kg(-1). Common 
      adverse events (AEs) included peripheral oedema, fatigue and nausea. Three 
      patients experienced grade ⩾3 treatment-related hyperkalaemia/hypokalaemia, 
      diarrhoea or fatigue. Best overall response (44%) was stable disease (SD); median 
      duration was 5.5 months (0.4-18.7 months). One patient has been on therapy with 
      SD for >4 years. Pharmacokinetics of ficlatuzumab showed low clearance 
      (0.17-0.26 ml h(-1) kg(-1)), a half-life of 6.8-9.4 days and dose-proportional 
      exposure. Ficlatuzumab/erlotinib had no impact on the PK of either agent. No ADAs 
      were detected. Ficlatuzumab increased serum HGF levels. CONCLUSIONS: Recommended 
      phase II dose is 20 mg kg(-1) q2w for ficlatuzumab monotherapy or with erlotinib. 
      Preliminary antitumour activity and manageable AEs were observed. 
      Pharmacokinetics were dose-proportional and consistent with other IgG 
      therapeutics. Ficlatuzumab was not immunogenic, and serum HGF was a potential PD 
      marker.
FAU - Patnaik, A
AU  - Patnaik A
AD  - Clinical Research, South Texas Accelerated Research Therapeutics (START), 4383 
      Medical Drive, San Antonio, TX 78229, USA.
FAU - Weiss, G J
AU  - Weiss GJ
AD  - Division of Hematology and Medical Oncology, Virginia G Piper Cancer Center, 
      10460 North 92nd Street, Suite 101, Scottsdale, AZ 85258, USA.
FAU - Papadopoulos, K P
AU  - Papadopoulos KP
AD  - Clinical Research, South Texas Accelerated Research Therapeutics (START), 4383 
      Medical Drive, San Antonio, TX 78229, USA.
FAU - Hofmeister, C C
AU  - Hofmeister CC
AD  - Hematology Division Internal Medicine Department, Ohio State University, 320 West 
      10th Avenue, Columbus, OH 43210, USA.
FAU - Tibes, R
AU  - Tibes R
AD  - Division of Hematology and Medical Oncology, Virginia G Piper Cancer Center, 
      10460 North 92nd Street, Suite 101, Scottsdale, AZ 85258, USA.
FAU - Tolcher, A
AU  - Tolcher A
AD  - Clinical Research, South Texas Accelerated Research Therapeutics (START), 4383 
      Medical Drive, San Antonio, TX 78229, USA.
FAU - Isaacs, R
AU  - Isaacs R
AD  - Merck, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
FAU - Jac, J
AU  - Jac J
AD  - AVEO Pharmaceuticals, Inc., 75 Sidney Street, Cambridge, MA 02139, USA.
FAU - Han, M
AU  - Han M
AD  - AVEO Pharmaceuticals, Inc., 75 Sidney Street, Cambridge, MA 02139, USA.
FAU - Payumo, F C
AU  - Payumo FC
AD  - AVEO Pharmaceuticals, Inc., 75 Sidney Street, Cambridge, MA 02139, USA.
FAU - Cotreau, M M
AU  - Cotreau MM
AD  - AVEO Pharmaceuticals, Inc., 75 Sidney Street, Cambridge, MA 02139, USA.
FAU - Ramanathan, R K
AU  - Ramanathan RK
AD  - Division of Hematology and Medical Oncology, Virginia G Piper Cancer Center, 
      10460 North 92nd Street, Suite 101, Scottsdale, AZ 85258, USA.
LA  - eng
GR  - P30 CA016058/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140605
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - 77E89833TG (ficlatuzumab)
RN  - DA87705X9K (Erlotinib Hydrochloride)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Cohort Studies
MH  - Erlotinib Hydrochloride
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/metabolism/pathology
MH  - Neoplasms/*drug therapy/metabolism/pathology
MH  - Protein Kinase Inhibitors/administration & dosage/pharmacokinetics
MH  - Quinazolines/administration & dosage/adverse effects/pharmacokinetics
PMC - PMC4102944
EDAT- 2014/06/06 06:00
MHDA- 2014/11/12 06:00
PMCR- 2015/07/15
CRDT- 2014/06/06 06:00
PHST- 2014/01/13 00:00 [received]
PHST- 2014/04/25 00:00 [revised]
PHST- 2014/05/07 00:00 [accepted]
PHST- 2014/06/06 06:00 [entrez]
PHST- 2014/06/06 06:00 [pubmed]
PHST- 2014/11/12 06:00 [medline]
PHST- 2015/07/15 00:00 [pmc-release]
AID - bjc2014290 [pii]
AID - 10.1038/bjc.2014.290 [doi]
PST - ppublish
SO  - Br J Cancer. 2014 Jul 15;111(2):272-80. doi: 10.1038/bjc.2014.290. Epub 2014 Jun 
      5.