targeted agent and profiling utilization · · 2018-03-29p h a 3 e r b b 4 a t m c r e b b p e g...
TRANSCRIPT
Targeted Agent and Profiling Utilization
Registry (TAPUR™) Study
March 2018
Precision Medicine• Therapies designed to target the molecular alteration that
aids cancer development T
P53
BR
AF
PIK
3C
AC
DK
N2A
KR
AS
NF
1E
PH
A3
ER
BB
4AT
MC
RE
BB
PE
GF
RE
PH
A5
PT
EN
RO
S1
NO
TC
H2
SM
AR
CA
4A
PC
KD
RM
LL
BR
CA
2N
OT
CH
1N
RA
SP
DG
FR
AAT
RD
DR
2E
ZH
2F
LT3
NT
RK
3R
B1
RE
TC
DH
1F
BX
W7
PIK
3R
1A
SX
L1
BC
L2
CT
NN
B1
ER
BB
2JA
K2
ME
TM
TO
RS
TK
11
CD
KN
1B
GN
AS
MA
P2
K1
SM
AD
4S
YK
AB
L1
BR
CA
1E
RB
B3
MY
CP
TC
H1
RU
NX
1A
LK
BR
D4
CD
K4
ER
GF
GF
R2
IGF
1R
MS
H2
MS
H6
NF
KB
IAA
KT
1E
TV
6P
DG
FR
BS
MO
TS
C2
WT
1X
PO
1A
RF
GF
R1
KIT
MD
M4
ME
N1
CD
KN
2B
CR
KL
MA
P2
K4
MD
M2
SM
AD
2T
ET
2B
AP
1C
CN
D1
CC
ND
2D
NM
T3A
ES
R1
ET
V1
EW
SR
1F
GF
R3
GN
AQ
HR
AS
IDH
1JA
K3
ML
H1
RA
F1
RA
RA
AU
RK
AB
RD
3C
CN
D3
CC
NE
1ID
H2
MA
P2
K2
MIT
FN
F2
TM
PR
SS
2T
SC
1V
HL
BR
D2
ET
V4
ET
V5
MP
LS
MA
RC
B1
AR
AF
GN
A11
MC
L1
NK
X2
−1
AK
T2
AK
T3
CD
K6
CD
KN
1A
CE
BPA
0
5
10
15
20
25
30
TA
RG
ET
ge
ne a
lte
ration
s (
%)
Rare (Less than 2%)Intermediate (2−5%)
Common (5% or greater)All
0 25 50 75 100
Patients with TARGET Gene events by category (%)
02
04
060
80
10
0
2005 2006 2007 2008 2009 2010 2011 2012
New
TA
RG
ET
Gen
e T
rials
Year
• A large proportion of cancers may contain at least one plausibly actionable genetic alteration
• The “long tail” means that the conventional clinical trial design approach may not be feasible
Van Allen, Wagle et al., Nature Med 20, 682–688 (2014)
Problems
• Patient with advanced cancer; no standard treatment
options
• Genomic profile test performed
• Potentially actionable aberration detected
• FDA-approved drug available for aberration
How to get the drug that might be beneficial?
How to learn from the treatment?
Overall Goals of TAPUR
Who Benefits?
Eligibility
TAPUR Study Primary Objective
• To describe the anti-tumor activity
and toxicity of commercially
available, targeted anti-cancer
drugs prescribed for treatment of
patients whose tumors have a
genomic variant known to be a drug
target, or to predict sensitivity to a
drug
Study Endpoints and Analysis
• Primary endpoint: ORR or SD at 16 weeks per relevant
response criteria
• Other endpoints: PFS, OS, time on treatment, grade 3-5
AEs per CTCAE, SAEs
• Each tumor type-variant-drug is a “group”
• Enroll 10 patients/group. If 1 or fewer responses, stop
• If at least 2 responses, enroll additional 18
• 7 or more responses/28, further study
How does TAPUR work?
Participating Pharmaceutical Companies
• Seven companies currently committed to participate
– Providing free drug (ongoing access for responders)
– Per-case payment for over 1200 TAPUR participants
– Infrastructure support for ASCO staff and study
administration
Supporting Vendors
• Syapse Precision Medicine
software
– Electronic data collection platform
and study workflows
• Cardinal Health Specialty
Pharmacy
– Central drug distribution
Key Milestones
• FDA reviewed and determined TAPUR Study IND-exempt (August 2015)
• TAPUR Study Launch (March 2016)
• Addition of new study therapy; lowered enrollment age to 12 years of age (May 2017)
• Opened collaborations with international research groups and molecular testing companies (June 2017)
• Over 100 clinical site locations enrolling participants (December 2017)
• 1000th participant registered (consented to study) (February 2018)
• 750th participant enrolled (on study drug treatment) (March 2018)
