PMID- 34785698
OWN - NLM
STAT- MEDLINE
DCOM- 20220126
LR  - 20230208
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Nov 16
TI  - A phase I study of the WT2725 dosing emulsion in patients with advanced 
      malignancies.
PG  - 22355
LID - 10.1038/s41598-021-01707-3 [doi]
LID - 22355
AB  - WT2725 is a Wilms' tumor gene 1 (WT1)-derived-oligopeptide vaccine designed to 
      induce WT1-specific cytotoxic T-lymphocytes against WT1(+) tumors in human 
      leukocyte antigen (HLA)-A*0201(+) and/or HLA-A*0206(+) patients. Here, we report 
      the results of a phase I study of WT2725. In this phase I, open-label, 
      dose-escalation and expansion two-part study, the WT2725 dosing emulsion was 
      administered as a monotherapy to patients with advanced malignancies known to 
      overexpress WT1, including glioblastoma. In part 1, 44 patients were sequentially 
      allocated to four doses: 0.3 mg (n = 5), 0.9 mg (n = 5), 3 mg (n = 6), and 9 mg 
      (n = 28). In part 2, 18 patients were allocated to two doses: 18 mg (n = 9) and 
      27 mg (n = 9). No dose-limiting toxicities were observed, so the maximum 
      tolerated dose was not reached. Median progression-free survival was 58 (95% 
      confidence interval [CI] 56-81) days (~ 2 months) across all patients with solid 
      tumors; median overall survival was 394 days (13.0 months) (95% CI 309-648). 
      Overall immune-related response rate in solid tumor patients was 7.5% (95% CI 
      2.6-19.9); response was most prominent in the glioblastoma subgroup. Overall, 
      62.3% of patients were considered cytotoxic T-lymphocyte responders; the 
      proportion increased with increasing WT2725 dosing emulsion dose. WT2725 dosing 
      emulsion was well tolerated. Preliminary tumor response and biological marker 
      data suggest that WT2725 dosing emulsion may exert antitumor activity in 
      malignancies known to overexpress the WT1 protein, particularly glioblastoma, and 
      provide a rationale for future clinical development.Trial registration: 
      NCT01621542.
CI  - (c) 2021. The Author(s).
FAU - Fu, Siqing
AU  - Fu S
AUID- ORCID: 0000-0002-1933-0419
AD  - Department of Investigational Cancer Therapeutics, The University of Texas MD 
      Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. 
      siqingfu@mdanderson.org.
FAU - Piccioni, David E
AU  - Piccioni DE
AD  - UCSD Moores Cancer Center, San Diego, CA, USA.
FAU - Liu, Hongtao
AU  - Liu H
AD  - University of Chicago Medical Center, Chicago, IL, USA.
FAU - Lukas, Rimas V
AU  - Lukas RV
AD  - Northwestern University, Chicago, IL, USA.
AD  - Lou and Jean Malnati Brain Tumor Institute, Chicago, IL, USA.
FAU - Kesari, Santosh
AU  - Kesari S
AD  - Saint John's Cancer Institute and Pacific Neuroscience Institute, Santa Monica, 
      CA, USA.
FAU - Aregawi, Dawit
AU  - Aregawi D
AD  - Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, 
      Hershey, PA, USA.
FAU - Hong, David S
AU  - Hong DS
AD  - Department of Investigational Cancer Therapeutics, The University of Texas MD 
      Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
FAU - Yamaguchi, Kenichiro
AU  - Yamaguchi K
AD  - Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan.
FAU - Whicher, Kate
AU  - Whicher K
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
FAU - Chen, Yu-Luan
AU  - Chen YL
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
FAU - Poola, Nagaraju
AU  - Poola N
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
AD  - Otsuka Pharmaceuticals, Princeton, NJ, USA.
FAU - Eddy, John
AU  - Eddy J
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
AD  - Morphic Therapeutic, Waltham, MA, USA.
FAU - Blum, David
AU  - Blum D
AD  - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01621542
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20211116
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cancer Vaccines)
RN  - 0 (Emulsions)
RN  - 0 (Oligopeptides)
RN  - 0 (WT1 Proteins)
RN  - 0 (WT1 protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cancer Vaccines/*administration & dosage/adverse effects/immunology
MH  - Disease-Free Survival
MH  - Emulsions
MH  - Female
MH  - *Glioblastoma/immunology/mortality/therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Oligopeptides/*administration & dosage/adverse effects/immunology
MH  - Survival Rate
MH  - WT1 Proteins/*immunology
PMC - PMC8595891
COIS- S.F. and D.A. have nothing to disclose. D.P. is part of the advisory 
      council/committee for AbbVie and Tocagen. H.L. received honoraria from Agios and 
      grants/funds from BMS and Karyopharm. R.L. served on a scientific advisory board 
      for Novocure, Monteris and AbbVie; served on the speakers bureau for Novocure; 
      received consulting fees from AbbVie, American Physician Institute, Medlink 
      Neurology, EBSCO Publishing, Eisai, and New Link Genetics; received a BrainUp 
      grant for Translational Approaches to Brain Tumors; and received research support 
      (drug only) from Bristol Myers Squibb. S.K. is an employee of Pacific 
      Neuroscience Institute, Providence Saint John's Health Center, John Wayne Cancer 
      Institute; owns stock/shares in Curtana and Nascent; received grants/funds from 
      Aivita, Diffusion, Boston Biomedical, Medicenna, Aadi, BI, Sanofi, Spectrum, 
      Novocure, Northwestern, Orbus Stellar, Prevlar (epicentrx), Stemedica, 
      EORTC-CTCG, EIP Pharma, Caris, Amgen (Omniseq, Guardant, Biocept, LJIAI). D.H. 
      owns stock/shares in OncoResponse Molecular Match (Advisor), OncoResponse 
      (Founder), and Presagia Inc (Advisor); is part of the advisory council/committee 
      and received consulting fees from Alpha Insights, Amgen, Axiom, Adaptimmune, 
      Baxter, Bayer, Genentech, GLG, Group H, Guidepoint, Infinity, Janssen, Merrimack, 
      Medscape, Numab, Pfizer, Prime Oncology, Seattle Genetics, Takeda, Trieza 
      Therapeutics, WebMD; received honoraria from LOXO, miRNA, Genmab, AACR, ASCO, and 
      SITC; received grants/funds from AbbVie, Adaptimmune, Aldi-Norte, Amgen, 
      Astra-Zeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, 
      Genmab, Ignyta, Infinity, Kite, Kyowa, Lilly, LOXO, Merck, Medimmune, Mirati, 
      miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfizer, Seattle 
      Genetics, Takeda, Turning Point Therapeutics. K.Y. is an employee of Sumitomo 
      Dainippon Pharma Co., Ltd. K.W., Y.Z., and Y.L.C. are employees of Sunovion 
      Pharmaceuticals Inc. N.P., J.E., and D.B. are former employees of Sunovion 
      Pharmaceuticals Inc. D.B. is a paid consultant of Sunovion Pharmaceuticals Inc.
EDAT- 2021/11/18 06:00
MHDA- 2022/01/27 06:00
PMCR- 2021/11/16
CRDT- 2021/11/17 06:25
PHST- 2020/12/10 00:00 [received]
PHST- 2021/10/19 00:00 [accepted]
PHST- 2021/11/17 06:25 [entrez]
PHST- 2021/11/18 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/11/16 00:00 [pmc-release]
AID - 10.1038/s41598-021-01707-3 [pii]
AID - 1707 [pii]
AID - 10.1038/s41598-021-01707-3 [doi]
PST - epublish
SO  - Sci Rep. 2021 Nov 16;11(1):22355. doi: 10.1038/s41598-021-01707-3.