PMID- 29982805
OWN - NLM
STAT- MEDLINE
DCOM- 20200501
LR  - 20231005
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 21
IP  - 1
DP  - 2019 Jan 1
TI  - Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with 
      EGFR-amplified, recurrent glioblastoma: results from an international phase I 
      multicenter trial.
PG  - 106-114
LID - 10.1093/neuonc/noy091 [doi]
AB  - BACKGROUND: Patients with glioblastoma (GBM) have a dismal prognosis. Nearly all 
      will relapse with no clear standard of care for recurrent disease (rGBM). 
      Approximately 50% of patients have tumors harboring epidermal growth factor 
      receptor (EGFR) amplification. The antibody-drug conjugate depatuxizumab 
      mafodotin (depatux-m) binds cells with EGFR amplification, is internalized, and 
      releases a microtubule toxin, killing the cell. Here we report efficacy, safety 
      and pharmacokinetics (PK) of depatux-m + temozolomide (TMZ) in patients with 
      EGFR-amplified rGBM. METHODS: M12-356 (NCT01800695) was an open-label study 
      encompassing patients with newly diagnosed or rGBM across 3 treatment arms. 
      Results are reported for adults with EGFR-amplified, measurable rGBM who received 
      depatux-m (0.5-1.5 mg/kg) on days 1 and 15, and TMZ (150-200 mg/m2) on days 1-5 
      in a 28-day cycle. Patients were bevacizumab and nitrosourea naive. RESULTS: 
      There were 60 patients, median age 56 years (range, 20-79). Fifty-nine patients 
      previously received TMZ. Common adverse events (AEs) were blurred vision (63%), 
      fatigue (38%), and photophobia (35%). Grades 3/4 AEs were split between ocular 
      and non-ocular AEs, occurring in 22% of patients each. Systemic PK exposure of 
      depatux-m was dose proportional. The objective response rate was 14.3%, the 
      6-month progression-free survival rate was 25.2%, and the 6-month overall 
      survival rate was 69.1%. CONCLUSIONS: Depatux-m + TMZ displayed an AE profile 
      similar to what was described previously. Antitumor activity in this 
      TMZ-refractory population was encouraging. Continued study of depatux-m in 
      patients with EGFR-amplified, newly diagnosed, or recurrent GBM is ongoing in 2 
      global, randomized trials (NCT02573324, NCT02343406).
FAU - Lassman, Andrew B
AU  - Lassman AB
AD  - Department of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia 
      University Irving Medical Center, New York, NY, USA.
FAU - van den Bent, Martin J
AU  - van den Bent MJ
AD  - Erasmus MC Cancer Institute, Rotterdam, Netherlands.
FAU - Gan, Hui K
AU  - Gan HK
AD  - School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia.
AD  - Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
AD  - Austin Health and Olivia Newton-John Cancer Research Institute, Melbourne, 
      Victoria, Australia.
FAU - Reardon, David A
AU  - Reardon DA
AD  - Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, 
      USA.
FAU - Kumthekar, Priya
AU  - Kumthekar P
AD  - Northwestern University, Chicago, Illinois, USA.
FAU - Butowski, Nicholas
AU  - Butowski N
AD  - Department of Neurological Surgery, University of California San Francisco, San 
      Francisco, California, USA.
FAU - Lwin, Zarnie
AU  - Lwin Z
AD  - Department of Medical Oncology, University of Queensland School of Medicine, 
      Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
FAU - Mikkelsen, Tom
AU  - Mikkelsen T
AD  - Henry Ford Health System, Detroit, Michigan, USA.
FAU - Nabors, Louis B
AU  - Nabors LB
AD  - University of Alabama at Birmingham, Birmingham, Alabama, USA.
FAU - Papadopoulos, Kyriakos P
AU  - Papadopoulos KP
AD  - South Texas Accelerated Research Therapeutics (START), San Antonio, Texas, USA.
FAU - Penas-Prado, Marta
AU  - Penas-Prado M
AD  - The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
FAU - Simes, John
AU  - Simes J
AD  - NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, 
      Australia.
FAU - Wheeler, Helen
AU  - Wheeler H
AD  - Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
FAU - Walbert, Tobias
AU  - Walbert T
AD  - Henry Ford Health System, Detroit, Michigan, USA.
FAU - Scott, Andrew M
AU  - Scott AM
AD  - School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia.
AD  - Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
AD  - Austin Health and Olivia Newton-John Cancer Research Institute, Melbourne, 
      Victoria, Australia.
FAU - Gomez, Erica
AU  - Gomez E
AD  - AbbVie Inc., North Chicago, Illinois, USA.
FAU - Lee, Ho-Jin
AU  - Lee HJ
AD  - AbbVie Inc., North Chicago, Illinois, USA.
FAU - Roberts-Rapp, Lisa
AU  - Roberts-Rapp L
AD  - AbbVie Inc., North Chicago, Illinois, USA.
FAU - Xiong, Hao
AU  - Xiong H
AD  - AbbVie Inc., North Chicago, Illinois, USA.
FAU - Ansell, Peter J
AU  - Ansell PJ
AD  - AbbVie Inc., North Chicago, Illinois, USA.
FAU - Bain, Earle
AU  - Bain E
AD  - AbbVie Inc., North Chicago, Illinois, USA.
FAU - Holen, Kyle D
AU  - Holen KD
AD  - AbbVie Inc., North Chicago, Illinois, USA.
FAU - Maag, David
AU  - Maag D
AD  - AbbVie Inc., North Chicago, Illinois, USA.
FAU - Merrell, Ryan
AU  - Merrell R
AD  - NorthShore University Health System, Evanston, Illinois, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01800695
SI  - ClinicalTrials.gov/NCT02573324
SI  - ClinicalTrials.gov/NCT02343406
GR  - P30 CA013148/CA/NCI NIH HHS/United States
GR  - UG1 CA189960/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - F3R7A4P04N (depatuxizumab mafodotin)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics/*therapeutic use
MH  - Brain Neoplasms/*drug therapy/genetics/pathology
MH  - Cohort Studies
MH  - ErbB Receptors/genetics
MH  - Female
MH  - Follow-Up Studies
MH  - *Gene Amplification
MH  - Glioblastoma/*drug therapy/genetics/pathology
MH  - Humans
MH  - International Agencies
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/genetics/pathology
MH  - Prognosis
MH  - Temozolomide/administration & dosage
MH  - Tissue Distribution
MH  - Young Adult
PMC - PMC6303422
EDAT- 2018/07/10 06:00
MHDA- 2020/05/02 06:00
PMCR- 2018/07/05
CRDT- 2018/07/09 06:00
PHST- 2018/07/10 06:00 [pubmed]
PHST- 2020/05/02 06:00 [medline]
PHST- 2018/07/09 06:00 [entrez]
PHST- 2018/07/05 00:00 [pmc-release]
AID - 5049251 [pii]
AID - noy091 [pii]
AID - 10.1093/neuonc/noy091 [doi]
PST - ppublish
SO  - Neuro Oncol. 2019 Jan 1;21(1):106-114. doi: 10.1093/neuonc/noy091.