PMID- 30425090
OWN - NLM
STAT- MEDLINE
DCOM- 20190703
LR  - 20231020
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 25
IP  - 8
DP  - 2019 Apr 15
TI  - Phase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in 
      Patients with Advanced Solid Tumors.
PG  - 2403-2413
LID - 10.1158/1078-0432.CCR-18-1341 [doi]
AB  - PURPOSE: This first-in-human, open-label phase I study evaluated AMG 337, an 
      oral, highly selective small-molecule inhibitor of MET in advanced solid 
      tumors.Patients and Methods: Patients enrolled into dose-escalation cohorts 
      received AMG 337 up to 400 mg once daily or up to 250 mg twice daily, following a 
      modified 3+3+3 design. Dose expansion was conducted in MET-amplified patients at 
      the maximum tolerated dose (MTD). Primary endpoints included assessment of 
      adverse events (AEs), establishment of the MTD, and pharmacokinetics; clinical 
      response was a secondary endpoint. RESULTS: The safety analysis set included 111 
      patients who received >/=1 dose of AMG 337. Thirteen patients had >/=1 AE qualifying 
      as dose-limiting toxicity. The MTD was determined to be 300 mg once daily; the 
      MTD for twice-daily dosing was not reached. Most frequent treatment-related AEs 
      were headache (63%) and nausea (31%). Grade >/=3 treatment-related AEs occurred in 
      23 patients (21%), most commonly headache (n = 6) and fatigue (n = 5). Maximum 
      plasma concentration occurred at 3.0 hours following 300-mg once-daily dosing, 
      indicating AMG 337 absorption soon after treatment. Objective response rate was 
      9.9% (11/111; 95% CI, 5.1%-17.0%) in all patients and 29.6% (8/27; 95% CI, 
      13.8%-50.2%) in MET-amplified patients; median (range) duration of response was 
      202 (51-1,430+) days in all patients and 197 (64-1,430+) days in MET-amplified 
      patients. CONCLUSIONS: Oral AMG 337 was tolerated with manageable toxicities, 
      with an MTD and recommended phase II dose of 300 mg once daily. The promising 
      response rate observed in patients with heavily pretreated MET-amplified tumors 
      warrants further investigation.See related commentary by Ma, p. 2375.
CI  - (c)2018 American Association for Cancer Research.
FAU - Hong, David S
AU  - Hong DS
AD  - Department of Investigational Cancer Therapeutics, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas. dshong@mdanderson.org.
FAU - LoRusso, Patricia
AU  - LoRusso P
AD  - Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
FAU - Hamid, Omid
AU  - Hamid O
AD  - Melanoma Center, The Angeles Clinic and Research Institute, Los Angeles, 
      California.
FAU - Janku, Filip
AU  - Janku F
AD  - Department of Investigational Cancer Therapeutics, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Kittaneh, Muaiad
AU  - Kittaneh M
AD  - Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, 
      Chicago, Illinois.
FAU - Catenacci, Daniel V T
AU  - Catenacci DVT
AD  - Hematology/Oncology, University of Chicago, Chicago, Illinois.
FAU - Chan, Emily
AU  - Chan E
AD  - Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
FAU - Bekaii-Saab, Tanios
AU  - Bekaii-Saab T
AD  - Department of Internal Medicine, Mayo Clinic, Phoenix, Arizona.
FAU - Gadgeel, Shirish M
AU  - Gadgeel SM
AD  - Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
AD  - Thoracic Oncology, Karmanos Cancer Institute, Detroit, Michigan.
AD  - Department of Internal Medicine, Division of Hematology/Oncology, University of 
      Michigan, Ann Arbor, Michigan.
FAU - Loberg, Robert D
AU  - Loberg RD
AD  - Oncology Biomarkers, Amgen Inc., Thousand Oaks, California.
FAU - Amore, Benny M
AU  - Amore BM
AD  - Clinical Pharmacology, Modeling and Simulation, Amgen Inc., South San Francisco, 
      California.
FAU - Hwang, Yuying C
AU  - Hwang YC
AD  - Global Biostatistical Sciences, Amgen Inc., Thousand Oaks, California.
FAU - Tang, Rui
AU  - Tang R
AD  - Global Biostatistical Sciences, Amgen Inc., Thousand Oaks, California.
FAU - Ngarmchamnanrith, Gataree
AU  - Ngarmchamnanrith G
AD  - Early Development, Hematology and Oncology, Amgen Inc., Thousand Oaks, 
      California.
FAU - Kwak, Eunice L
AU  - Kwak EL
AD  - Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, 
      Massachusetts.
LA  - eng
GR  - P30 CA022453/CA/NCI NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20181113
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (AMG 337)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridones)
RN  - 0 (Triazoles)
SB  - IM
CIN - Clin Cancer Res. 2019 Apr 15;25(8):2375-2378. PMID: 30770350
MH  - Humans
MH  - Maximum Tolerated Dose
MH  - *Neoplasms
MH  - *Protein Kinase Inhibitors
MH  - Pyridones
MH  - Treatment Outcome
MH  - Triazoles
PMC - PMC6892342
MID - NIHMS1060528
EDAT- 2018/11/15 06:00
MHDA- 2019/07/04 06:00
PMCR- 2020/04/15
CRDT- 2018/11/15 06:00
PHST- 2018/04/30 00:00 [received]
PHST- 2018/08/28 00:00 [revised]
PHST- 2018/11/08 00:00 [accepted]
PHST- 2018/11/15 06:00 [pubmed]
PHST- 2019/07/04 06:00 [medline]
PHST- 2018/11/15 06:00 [entrez]
PHST- 2020/04/15 00:00 [pmc-release]
AID - 1078-0432.CCR-18-1341 [pii]
AID - 10.1158/1078-0432.CCR-18-1341 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2019 Apr 15;25(8):2403-2413. doi: 10.1158/1078-0432.CCR-18-1341. 
      Epub 2018 Nov 13.