PMID- 24633809
OWN - NLM
STAT- MEDLINE
DCOM- 20140818
LR  - 20191210
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 73
IP  - 5
DP  - 2014 May
TI  - A Phase Ib study evaluating MNRP1685A, a fully human anti-NRP1 monoclonal 
      antibody, in combination with bevacizumab and paclitaxel in patients with 
      advanced solid tumors.
PG  - 951-60
LID - 10.1007/s00280-014-2426-8 [doi]
AB  - PURPOSE: MNRP1685A is a human monoclonal antibody that blocks binding of vascular 
      endothelial growth factor (VEGF), VEGF-B, and placental growth factor 2 to 
      neuropilin-1 resulting in vessel immaturity and VEGF dependency. The safety of 
      combining MNRP1685A with bevacizumab, with or without paclitaxel, was examined. 
      METHODS: Patients with advanced solid tumors received escalating doses of 
      MNRP1685A (7.5, 15, 24, and 36 mg/kg) with bevacizumab 15 mg/kg every 3 weeks in 
      Arm A (n = 14). Arm B (n = 10) dosing consisted of MNRP1685A (12 and 16 mg/kg) 
      with bevacizumab 10 mg/kg (every 2 weeks) and paclitaxel 90 mg/m(2) (weekly, 3 of 
      4 weeks). Objectives were to determine safety, pharmacokinetics, 
      pharmacodynamics, and the maximum tolerated dose of MNRP1685A. RESULTS: Infusion 
      reactions (88 %) and transient thrombocytopenia (67 %) represent the most 
      frequent study drug-related adverse events (AEs). Drug-related Grade 2 or 3 
      proteinuria occurred in 13 patients (54 %). Additional study drug-related AEs 
      occurring in >20 % of patients included neutropenia, alopecia, dysphonia, 
      fatigue, and nausea. Neutropenia occurred only in Arm B. Grade >/=3 study 
      drug-related AEs in >/=3 patients included neutropenia (Arm B), proteinuria, and 
      thrombocytopenia. Two confirmed and three unconfirmed partial responses were 
      observed. CONCLUSIONS: The safety profiles were consistent with the single-agent 
      profiles of all study drugs. However, a higher than expected rate of clinically 
      significant proteinuria was observed that does not support further testing of 
      MNRP1685A in combination with bevacizumab.
FAU - Patnaik, Amita
AU  - Patnaik A
AD  - South Texas Accelerated Research Therapeutics, 4383 Medical Drive, San Antonio, 
      TX, 78229, USA, amita.patnaik@start.stoh.com.
FAU - LoRusso, Patricia M
AU  - LoRusso PM
FAU - Messersmith, Wells A
AU  - Messersmith WA
FAU - Papadopoulos, Kyriakos P
AU  - Papadopoulos KP
FAU - Gore, Lia
AU  - Gore L
FAU - Beeram, Muralidhar
AU  - Beeram M
FAU - Ramakrishnan, Vanitha
AU  - Ramakrishnan V
FAU - Kim, Amy H
AU  - Kim AH
FAU - Beyer, Joseph C
AU  - Beyer JC
FAU - Mason Shih, L
AU  - Mason Shih L
FAU - Darbonne, Walter C
AU  - Darbonne WC
FAU - Xin, Yan
AU  - Xin Y
FAU - Yu, Ron
AU  - Yu R
FAU - Xiang, Hong
AU  - Xiang H
FAU - Brachmann, Rainer K
AU  - Brachmann RK
FAU - Weekes, Colin D
AU  - Weekes CD
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140317
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 144713-63-3 (Neuropilin-1)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 7SF22186WT (vesencumab)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/administration & dosage/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal/administration & dosage/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/adverse effects/pharmacokinetics/*therapeutic 
      use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Bevacizumab
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/metabolism/pathology
MH  - Neuropilin-1/administration & dosage/*therapeutic use
MH  - Paclitaxel/adverse effects/pharmacokinetics/*therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2014/03/19 06:00
MHDA- 2014/08/19 06:00
CRDT- 2014/03/18 06:00
PHST- 2014/01/21 00:00 [received]
PHST- 2014/02/23 00:00 [accepted]
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2014/08/19 06:00 [medline]
AID - 10.1007/s00280-014-2426-8 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2014 May;73(5):951-60. doi: 
      10.1007/s00280-014-2426-8. Epub 2014 Mar 17.