PMID- 25777467
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20221207
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 33
IP  - 3
DP  - 2015 Jun
TI  - Phase I study of the anti-MET antibody onartuzumab in patients with solid tumors 
      and MET-positive lung cancer.
PG  - 632-40
LID - 10.1007/s10637-015-0227-5 [doi]
AB  - Onartuzumab is a monovalent, humanized, monoclonal antibody that showed 
      significant survival benefits in combination with erlotinib in MET-positive 
      non-small-cell lung cancer (NSCLC) in pre-specified subgroup analyses of a 
      randomized phase II study. We conducted a two-stage, open-label, multicenter, 
      phase I study of onartuzumab in Japanese patients. Stage 1 investigated the 
      safety, tolerability, pharmacokinetics (PK), and recommended dose of onartuzumab 
      in patients with solid tumors, and Stage 2 determined the safety, tolerability, 
      and PK of onartuzumab plus erlotinib in patients with MET-positive NSCLC. Nine 
      patients received onartuzumab monotherapy (4, 15, or 30 mg/kg on Day 1 of each 
      21-day cycle) in Stage 1, and six patients received onartuzumab (15 mg/kg) plus 
      erlotinib (150 mg/day) in Stage 2. There were no dose-limiting toxicities in 
      either stage. Serious adverse events (AEs) occurred in one patient in Stage 1 
      (convulsion), and two patients in Stage 2 (once case each of diarrhea, vomiting, 
      and pulmonary embolism), but there were no grade 4 AEs or AEs leading to death. 
      Onartuzumab PKs were linear in the dose range of 4 to 30 mg/kg, and were not 
      affected by co-administration with erlotinib. PK parameters of onartuzumab were 
      similar to those reported in non-Japanese patients. A partial response was 
      observed in a patient with MET immunohistochemistry 3+ NSCLC without MET gene 
      amplification. Based on these results, the recommended dose of onartuzumab in 
      Japanese patients with solid tumors is 15 mg/kg every 21 days. The combination of 
      onartuzumab with erlotinib is feasible in Japanese patients with MET-positive 
      lung cancer.
FAU - Nishio, Makoto
AU  - Nishio M
AD  - Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese 
      Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo, 135-8550, Japan, 
      mnishio@jfcr.or.jp.
FAU - Horiike, Atsushi
AU  - Horiike A
FAU - Nokihara, Hiroshi
AU  - Nokihara H
FAU - Horinouchi, Hidehito
AU  - Horinouchi H
FAU - Nakamichi, Shinji
AU  - Nakamichi S
FAU - Wakui, Hiroshi
AU  - Wakui H
FAU - Ohyanagi, Fumiyoshi
AU  - Ohyanagi F
FAU - Kudo, Keita
AU  - Kudo K
FAU - Yanagitani, Noriko
AU  - Yanagitani N
FAU - Takahashi, Shunji
AU  - Takahashi S
FAU - Kuboki, Yasutoshi
AU  - Kuboki Y
FAU - Yamamoto, Noboru
AU  - Yamamoto N
FAU - Yamada, Yasuhide
AU  - Yamada Y
FAU - Abe, Masaichi
AU  - Abe M
FAU - Tahata, Takashi
AU  - Tahata T
FAU - Tamura, Tomohide
AU  - Tamura T
LA  - eng
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 - 20150318
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antibodies, Monoclonal)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - MS1J9720WC (onartuzumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/adverse effects/blood/pharmacokinetics/*therapeutic use
MH  - Asian People
MH  - Dose-Response Relationship, Drug
MH  - Erlotinib Hydrochloride/therapeutic use
MH  - Female
MH  - Gene Dosage
MH  - Humans
MH  - Lung Neoplasms/blood/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Proto-Oncogene Proteins c-met/*antagonists & inhibitors/blood/genetics
MH  - Treatment Outcome
EDAT- 2015/03/18 06:00
MHDA- 2016/02/18 06:00
CRDT- 2015/03/18 06:00
PHST- 2014/12/17 00:00 [received]
PHST- 2015/03/04 00:00 [accepted]
PHST- 2015/03/18 06:00 [entrez]
PHST- 2015/03/18 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
AID - 10.1007/s10637-015-0227-5 [doi]
PST - ppublish
SO  - Invest New Drugs. 2015 Jun;33(3):632-40. doi: 10.1007/s10637-015-0227-5. Epub 
      2015 Mar 18.