Join Dr. O’Dwyer for an exciting webinar on the National Cancer Institute-MolecularAnalysis for Therapy Choice trial, (NCI-MATCH or EAY131) This phase II precision medicine trial is currently available at more than 1000 locations around the United States, allowing many patients to enroll at a facility close to home

1. Trial Update: NCI-MATCH
Our webinar will begin shortly.
WELCOME!

2. • Speaker: Dr. Peter O’dwyer
• Archived Webinars: FightColorectalCancer.org/Webinars
• AFTER THE WEBINAR: Expect an email with links to the
material & a survey. If you fill it out, we’ll send you an “I
booty” bracelet.
• Ask a question in the panel on the RIGHT SIDE of your
screen
• Follow along via Twitter – use the hashtag #CRCWebinar
Today’s Webinar:

3. Resources:

4. Disclaimer
:
The information and services provided by Fight Colorectal
Cancer are for general informational purposes only. The
information and services are not intended to be substitutes
for professional medical advice, diagnoses or treatment.
If you are ill, or suspect that you are ill, see a doctor
immediately. In an emergency, call 911 or go to the nearest
emergency room.
Fight Colorectal Cancer never recommends or endorses any
specific physicians, products or treatments for any condition.

5. Speaker:
Peter O’Dwyer, MD, is a Professor of Medicine at the
Hospital of the University of Pennsylvania and the
Presbyterian Medical Center of Philadelphia. Dr.
O’Dwyer received his MD from The University of
Dublin, Trinity College Dublin, Ireland, in 1975. He was
a Resident in Pediatrics from Waterbury Hospital,
Waterbury, Connecticut (1976-1979), and a Resident
in Internal Medicine, Greater Baltimore Medical Center,
Baltimore, Maryland (1979-1981). He went on to a
Fellowship in Oncology at The Baltimore Cancer
Research Cancer, University of Maryland Hospital. Dr.
O’Dwyer is a Fellow in the American College of
Physicians, and a member of the American Boards of
Pediatrics, American Boards of Internal Medicine, and
Subspecialty Boards in Medical Oncology.

6. Peter J. O’Dwyer, MD (U Pennsylvania)
ECOG-ACRIN Study Co-Chair
Version Date: 10/20/2016

7. Keith T. Flaherty1, Alice P. Chen2, Peter J. O'Dwyer3, Barbara A.
Conley2, Stanley R. Hamilton4, Mickey Williams5, Robert J.
Gray6, Shuli Li6, Lisa M. McShane6, Lawrence V. Rubinstein2,
Susanna I. Lee1, Constantine A. Gatsonis7, Frank I. Lin8, Paolo
F. Caimi9, Shaji Kumar10, Edith P. Mitchell11, James A. Zwiebel2,
A. John Iafrate1, Jeffrey Sklar12, Carlos L. Arteaga13
1Massachusetts General Hospital, Boston, MA; 2National Cancer Institute (NCI), Division of Cancer Treatment
and Diagnosis, Bethesda, MD; 3University of Pennsylvania, Philadelphia, PA; 4MD Anderson Cancer Center,
Houston, TX; 5 NCI Frederick National Laboratory for Cancer Research, Frederick, MD; 6Dana-Farber Cancer
Institute, Boston, MA; 7Brown University, Providence, RI, 8NCI Cancer Imaging Program, Rockville, MD 9Case
Western Reserve University, Cleveland, OH, 10Mayo Clinic, Rochester, MN, 11Thomas Jefferson University,
Philadelphia, PA. 12Yale University, New Haven, CT, 13Vanderbilt University, Nashville, TN
NCI-Molecular Analysis for Therapy Choice
(NCI-MATCH / EAY131)

8. 810/20/2016
What is NCI-MATCH?

9. 910/20/2016
NCI-MATCH Tumor Gene Testing

10. 1010/20/2016
NCI-MATCH Enrollment Expectations
Expected
match rate
= one in
every four
to five
patients
(23%)

11. 1110/20/2016
NCI-MATCH Objective
• To determine whether matching certain drugs or drug
combinations in adults whose tumors have specific gene
abnormalities will effectively treat their cancer, regardless
of the cancer type
• NCI-MATCH is a signal-finding trial
• Treatments that show promise can advance to larger,
more definitive trials

12. 1210/20/2016
Who is Eligible for NCI-MATCH Tumor Gene Testing?
• Adults ≥ 18 years of age
• Solid tumor or lymphoma whose disease has progressed
following at least one line of standard systemic therapy
– Or with a rare tumor that does not have standard therapy
– Myeloma eligible if tumor tissue available (fresh or archived)
o Those with bone marrow aspirates will soon be eligible (assay is now
validated across lab network and a protocol amendment is in process)
• ECOG performance status zero or one
• Adequate organ function
• Physicians are encouraged to select only those patients
able to tolerate being off treatment up to six weeks

13. 1310/20/2016
NCI-MATCH Step-by-Step Diagram

14. 1410/20/2016
NCI-MATCH Wait Times for Patients
Processing Step
Median
Business Days
Tumor sample submission from sites to EA central lab at
MD Anderson Cancer Center
7
Completion of tumor testing by lab network and return
of results to site
13
Further eligibility evaluation for patients assigned to a
treatment arm
14

15. 1510/20/2016
• Opened trial on August 12, 2015, with 10 treatment arms
• Paused screening of new patients on November 11,
2015, for planned interim analysis
• Continued development of treatment arms during pause
• Expanded to 17 arms on February 25, 2016, and re-
evaluated patients with matching tumor gene
abnormalities
• Resumed registration of new patients on May 31, 2016,
with 24 treatment arms
NCI-MATCH Trial Milestones

16. 1610/20/2016
NCI-MATCH Current Enrollment Status
• There are 230 patients enrolled for treatment as of
October 16, 2016, with each treatment arm seeking to
enroll 35 patients

17. 1710/20/2016
NCI-MATCH Availability
• This is a nationwide trial that is locally available at
community hospitals as well as at large cancer centers
• New sites continue to join
• There is some restriction on which sites can participate
–Must use the NCI’s Central Institutional Review Board,
for example
–Not available outside the US
• Visit cancer.gov or clinicaltrials.gov for locations

18. 1810/20/2016
NCI-MATCH Participation from 1K+ US Sites

19. 1910/20/2016
NCI-MATCH 24 Treatment Arms
I. Taselisib - PIK3CA mut
Z1B. Palbociclib - CCND1, 2, 3 amp & Rb protein exp via IHC
W. AZD4547 - FGFR pathway aberrations
P. GSK2636771 - PTEN loss by IHC
S1. Trametinib - NF1 mut
Q. Ado-trastuzumab emtansine for HER2 amp
Y. AZD5363 - AKT mut
Z1A. Binimetinib - NRAS mut
U. Dafactinib - NF2 loss
N. GSK2636771 - PTEN mut/del w exp on IHC
C1. Crizotinib - MET amp
B. Afatinib - HER2 activating mut
H. Dabrafenib+trametinib - BRAF V600E or V600K mut
T. Vismodegib - SMO or PTCH1 mut
R. Trametinib - BRAF fus or non V600E, nonV600K BRAF mut
E. AZD 9291 - EGFR T790M or rare EGFR activating mut
F. Crizotinib - ALK transloc
V. Sunitinib - cKIT mut
A. Afatinib - EGFR activating mut
X. Dasatinib - DDR2 mut
G. Crizotinib - ROS1 transloc
S2. Trametinib - GNAQ or GNA11 mut
C2. Crizotinib - MET exon 14 deletion
Z1D. Nivolumab - dMMR status
0
0
0
0
No data
No data
Arm ID - Drug(s) - Target Abnormality Predicted Prevalence Based on Rates Found in Interim Analysis

20. 2010/20/2016
NCI-MATCH Projected Match Rates and Enrollments
for 24 Treatment Arms
Arm / Target Expected
Match
Rate %
Expected
Enroll-
ment
Arm / Target Expected
Match
Rate %
Expected
Enroll-
ment
I PIK3CA mut 4.0 89 B ERBB2 mut 0.8 20
Z1B CCND1 amp 3.6 79 H BRAF V600 0.8 19
W FGFR1/2/3 2.9 65 T SMO/PTCH1 0.6 14
P PTEN loss 2.5 55 R BRAF non V600 0.3 8
Q ERBB2 amp 1.7 44 E EGFR T790M 0.2 4
S1 NF1 mut 1.9 41 F ALK transloc 0.2 4
Z1C CDK4/6 amp 1.7 38 V cKIT mut 0.2 3
Y AKT1 mut 1.2 28 A EGFR mut 0 0
Z1A NRAS mut 1.2 28 G ROS1 transloc 0 0
U NF2 loss 1.1 26 S2 GNAQ/GNA11 0 0
N PTEN mut 1.1 24 C2 MET ex 14 sk No Data Not Known
C1 MET amp 0.9 21 Z1D dMMR No Data Not Known
Expected Overall Match Rate = 23%

21. 2110/20/2016
Strategies to Identify Patients for Treatment Arms
that Address Rare Mutations
• Many existing and planned treatment arms target gene
abnormalities with prevalence rates lower than the literature
indicated when the trial was conceived; accrual strategies are
being developed for arms with rates of 2% or less
• We hope to increase enrollment to these arms by:
– Increasing the participation of cancer centers currently
performing tumor testing in people with advanced cancer
– Collaborating with commercial sequencing labs to notify
ordering physicians of relevant NCI-MATCH treatment arms
for their patients who have matching mutations

22. 2210/20/2016
NCI-MATCH Conclusions from the Interim Analysis
1. A trial of therapy based on genetic characteristics of the
tumor is feasible on a national scale in the NCI-sponsored
networks
– Unprecedented with registration higher than for any
other NCTN trial to date
2. The whole process of tumor characterization from accrual
to biology read-out is feasible, having been accomplished
in 87% of patients
3. A high proportion of less common malignancies in this early
analysis opens options for advances in these cancers

23. 2310/20/2016
NCI-MATCH Conclusions Cont’d
4. The interim analysis that was applied early in the trial
permitted implementation of several enhancements to the
structure of the study
5. The trial’s early analysis permits planning for the realistic
needs of additional trials/drugs that can be analyzed in
specific gene abnormalities

24. 2410/20/2016
NCI-MATCH Summary of Changes
• Main changes
– Increase in screening goal to 5,000 patients
– Expansion to 24 treatment arms
• 6+ more arms are in development
– Greater focus on communication to influence patient selection
– More lab capacity to accelerate return of results for patients
• Other changes
– Mandating needle aspiration in all cases
– Allowance of tumor samples obtained up to six months prior to
registration
– Allowance of data from other genetic platforms

25. 2510/20/2016
NCI-MATCH Primary Disease Sites of Patients
Screened as of August 14, 2016
Disease Site # Enrolled for Screening % (N=1702)
Colorectal 236 13.8
Breast 222 13.0
Non-Small Cell Lung 127 7.4
Prostate 40 2.3
Common Cancers Subtotal 625 36.5
Ovarian 178 10.4
Pancreas (Adeno/NOS) 100 5.8
Head and Neck 78 4.5
Endometrial/Uterine (Non-Sarcoma) 68 3.9
Esophageal/GE Junction/Gastric 58 3.4
Neuroendocrine 50 2.9
Cholangio 47 2.7
Bladder/Urinary Tract 40 2.3
Endometrial/Uterine Sarcoma 43 2.5
Small Cell Lung 32 1.8
Other 333 19.5
Primary Site Not Specified 53 3.1
Uncommon Cancers Subtotal 1,077 63.5

26. 2610/20/2016
NCI-MATCH Summary Statements
• Rapid pace of new patients registering for tumor testing continues,
with as many as 130 patients registering for screening in some
weeks
• Laboratory network routinely outperforms the industry average of
~80% for tumor gene testing completion rate, delivering a rate of
94% in one recent week
• The assay for bone marrow specimens is now validated across the
lab network, and we are processing a trial amendment

27. 2710/20/2016
Resources for NCI-MATCH
Main Webpages: cancer.gov/nci-match
ecog-acrin.org/nci-match-eay131
Protocol Documents: ctsu.org (password required)
Spanish: cancer.gov/espanol/nci-match
Email Inquiries: match@jimmy.harvard.edu
NCI’s Cancer Information Service:
1-800-4-CANCER and cancer.gov/contact
05/06/2016 27

28. 2810/20/2016
Advocate Involvement in NCI-MATCH
• Advocates helped design trial and are overseeing its conduct
• Patient Advocate Working Group provides input on
educational materials and PR efforts
• Gives study leadership insight and feedback from patients
and the advocate community
• Addresses questions and needs as they arise

29. Thank you for your attention.
I welcome your questions!

30. Question & Answer:
SNAP A
#STRONGARMSELFIE
Bayer HealthCare will donate $1 for every
photo posted (up to $25,000).
Flex a “strong arm” & post it to Twitter or
Instagram! (Use the hashtag!)

31. Join us for our next webinar:
Genetics and YOU
In this webinar, Fight CRC Medical Advisory Board
member, Heather Hampel, MS, CGC, will discuss the
major subtypes of hereditary colon cancer, the types
of genetic tests that by be useful for you and your
family, and what to do with your test results.
November 8, 2016
2:00ET/1:00CT/11:00PT