to clinical trials for children with cancer Charles Keller MD Scientific Director Moonshot Regional Summit Ad Hoc Preclinical Consortia to Support Trial Design Michelle Monje Stanford Jacques Grill ID: 812689
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Slide1
accelerating basic science discovery to clinical trials for children with cancer
Charles Keller MDScientific Director
Moonshot Regional Summit
Slide2Ad Hoc Preclinical Consortia to Support Trial Design
Michelle
Monje
Stanford;
Jacques Grill
Institut
Gustave-Roussy
;
Oren Becher
Duke;
Xiao-Nan Li
Baylor;
Maryam Fouladi
Cincinnati Children’s;
Ranadip Pal & Noah Berlow
Texas Tech;
Cynthia Hawkins
University of Toronto;
Esther Hulleman & D.G. Van Vuurden
VU Univ. Med.
Ctr
;
Eric Raabe & Kathy Warren
Johns Hopkins/NCI
; Catie Grasso, Paul Spellman
OHSU;
Marta Alonso
Madrid;
Amar Gajjar
St Jude;
Charles Keller
cc-TDI
Slide3a chemotherapy indifferent disease
that responds only transiently to radiation
a
nd
a tight spot for a Cancer.
Diffuse Intrinsic Brain Stem Gliomas
are treatable
…but
have never been Curable
Slide4for dipg,
to move the most effective targeted therapy combination to early phase clinical trials
in a period less than 18-24 monthsusing biomarker and functional assay evidence.the mission
Slide5experimental approach
Primary Culture
Molecular Credentialing
Single-Agent & Combination Screen
PPTP-friendly
Preclinical Screen
Slide6p
articipants
Michelle
Monje
Stanford
Jacques Grill
Institut
Gustave-Roussy
Xiao-Nan Li
Baylor
Dannis G. van Vuurden
Esther Hulleman
VU Cancer Center Amsterdam
Cynthia Hawkins
Sick Kids
Catie Grasso
Paul Spellman
Charles Keller
OHSU
Oren Becher
Duke
Eric Raabe
Kathy Warren
Paul Meltzer
JHMI/NCI
Ranadip Pal
Noah Berlow
Texas Tech
Slide7faces of the biology teams
Jinu Abraham
Lara Davis
Elaine Huang
Matthew Svalina
Nathalène
Truffaux
Jacques Grill
Ludivine LE DRET
Harpreet
Kaur, Eric
Raabe
, Isabella Taylor, (Marianne Hutt)
Yujie (Danny) Tang Lining Liu
Anitha
Ponnuswami
Spenser Chen
Michelle
Monje
Oren
Becher
Kristin Schroeder
Slide8more faces of the teams
Paul Spellman Catie Grasso
(Michael Quist)
Ranadip Pal Noah Berlow
Xiao-Nan Li with Mari
Kogiso
, Patricia Baxter,
Qi
Lin, Yue Wang, Hua Mao
Esther Hulleman
Dannis
van
Vuurden
Cynthia Hawkins
(and team)
Slide9The community is our sponsors
weekly public reporting:
http://pptiohsu.blogspot.com/2011/12/open-science-forum-dipg-preclinical.html
Slide10project &
timelime
2 drug DIPG combination
trial
COG CNS Symposium
Mar 2011
Funding
Nov 2011 –
Jan 2012
drug
plate v1.0
Jan 2012
Σ
samples
1
st
DNA
seq
June 2012
v2 plates
Sep 2012
choose combo’s
Apr 2013
mouse studies
May 2013
Sep 2013
final RNA, DNA sequencing
Apr 2013
partial
seq
results
Sep 2012
partial
completion
mice
studies
Sep 2014
Slide11Hits:
HDACi
and
CDKi
*
*
Slide12Hits:
HDACi
and
CDKi
Slide13IBs-W0128DIPG/Li15-18
panobinostat
10mg/kg/dose IP (arrows)
8.5
yo
M, Gr IV
XRT +TMZ+
Avastin
(18
mo
survival)
H3F3A gain; ACVR1 G328E; HDAC4 gain
SU-DIPG-VI (14 days)
control
panobinostat
10mg/kg/day IP
7yo F, Gr IV
XRT+SAHA (6
mo
survival)
H3F3A K27M; TP53 E198/R175H
panobinostat
in vivo
Slide14a splash, but working beyond that, too
Slide15Community
Parntership
works!PBTC Phase I dose escalation trial Novartis approved supplying drugbetter combination to be founddelivery is a serious question PK/PD will be key
Next steps