PMID- 25525888
OWN - NLM
STAT- MEDLINE
DCOM- 20150825
LR  - 20181202
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 5
IP  - 22
DP  - 2014 Nov 30
TI  - A phase 1b, open-label study of trebananib plus bevacizumab or motesanib in 
      patients with solid tumours.
PG  - 11154-67
AB  - BACKGROUND: To examine the angiopoietin pathway inhibitor trebananib IV plus the 
      anti-VEGF agents bevacizumab or motesanib in advanced solid tumours. METHODS: In 
      this open-label phase 1b study, patients received IV trebananib 3 mg kg-1 QW plus 
      bevacizumab 15 mg kg-1 Q3W (cohort 1) or motesanib orally 75 mg (cohort 2); or 
      trebananib 10 mg kg-1 plus bevacizumab 15 mg kg-1 (cohort 3) or motesanib 125 mg 
      (cohort 4). If <33% of patients had dose-limiting toxicities (DLTs), dose 
      escalation occurred. Endpoints were treatment-related adverse events (AEs) 
      incidence and pharmacokinetics (primary); anti-trebananib antibodies, biomarkers, 
      and tumour response (secondary). RESULTS: Thirty-six patients received >/= 1 dose 
      of trebananib (cohorts 1, 2, 3, 4; n = 6, 8, 19, 3). DLT of G3 intestinal 
      perforation and G3 tumor haemorrhage occurred in cohorts 2 and 3, respectively 
      (both n = 1). Across both trebananib plus bevacizumab cohorts, the most common 
      AEs included fatigue (n = 8), diarrhoea (n =4), constipation (n = 3), nausea (n = 
      3), and epistaxis (n = 3). Three patients across those cohorts had grade >/= 3 AEs. 
      Across the trebananib plus motesanib cohorts, the most common AEs included 
      hypertension (n = 4), diarrhoea (n = 4), nausea (n = 3), fatigue (n = 3), 
      vomiting (n = 2), and decreased appetite (n = 2). Two patients had grade >/= 3 AEs. 
      Trebananib did not markedly affect motesanib pharmacokinetics. Across the 
      trebananib plus bevacizumab cohorts, two patients had a partial response; 11 
      patients had stable disease lasting >6 months. Across the trebananib plus 
      motesanib cohorts, one patient had a partial response; five patients had stable 
      disease lasting >6 months. CONCLUSION: Trebananib IV 3 mg kg-1 or 10 mg kg-1 plus 
      bevacizumab or motesanib in advanced solid tumours may be associated with less 
      severe toxicities relative to those emerging when combining two anti-VEGF agents.
FAU - Hong, David S
AU  - Hong DS
AD  - Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, 
      University of Texas MD Anderson Cancer Center, Houston, TX 77230-1402, USA.
FAU - Kurzrock, Razelle
AU  - Kurzrock R
AD  - Center for Personalized Cancer Therapy and CTO, Division of Hematology and 
      Oncology, UC San Diego Moores Cancer Center, La Jolla, CA 92093-0658, USA.
FAU - Mulay, Marilyn
AU  - Mulay M
AD  - Mulay Educational and Clinical Consulting Associates, Los Angeles, CA 90025, USA.
FAU - Rasmussen, Erik
AU  - Rasmussen E
AD  - Department of Biostatistics, Amgen Inc., Thousand Oaks, CA 91320, USA.
FAU - Wu, Benjamin M
AU  - Wu BM
AD  - Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA 
      91320, USA.
FAU - Bass, Michael B
AU  - Bass MB
AD  - Department of Molecular Sciences and Computational Biology, Amgen Inc., Thousand 
      Oaks, CA 91320, USA.
FAU - Zhong, Zhandong D
AU  - Zhong ZD
AD  - Department of Clinical Immunology and Biological Sample Management, Amgen Inc., 
      Thousand Oaks, CA 91320, USA.
FAU - Friberg, Greg
AU  - Friberg G
AD  - Department of Early Development, Amgen Inc., Thousand Oaks, CA 91320, USA.
FAU - Rosen, Lee S
AU  - Rosen LS
AD  - Department of Medicine, Division of Hematology and Oncology, UCLA, Santa Monica, 
      CA 90404, USA.
LA  - eng
GR  - UL1 TR000371/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Indoles)
RN  - 0 (Oligonucleotides)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - F60NE4XB53 (imetelstat)
RN  - X8Y5U6NC7E (trebananib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Bevacizumab
MH  - Cohort Studies
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Indoles/administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Niacinamide/administration & dosage/adverse effects/analogs & derivatives
MH  - Oligonucleotides
MH  - Recombinant Fusion Proteins/administration & dosage/adverse effects
PMC - PMC4294348
EDAT- 2014/12/20 06:00
MHDA- 2015/08/26 06:00
PMCR- 2014/11/01
CRDT- 2014/12/20 06:00
PHST- 2014/06/19 00:00 [received]
PHST- 2014/10/02 00:00 [accepted]
PHST- 2014/12/20 06:00 [entrez]
PHST- 2014/12/20 06:00 [pubmed]
PHST- 2015/08/26 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - 2568 [pii]
AID - 10.18632/oncotarget.2568 [doi]
PST - ppublish
SO  - Oncotarget. 2014 Nov 30;5(22):11154-67. doi: 10.18632/oncotarget.2568.