Trial Update: NCI-MATCH

Our webinar will begin shortly.

WELCOME!

• 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:

Resources:

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.

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.

Peter J. O’Dwyer, MD (U Pennsylvania)ECOG-ACRIN Study Co-Chair

Version Date: 10/20/2016

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)

810/20/2016

What is NCI-MATCH?

910/20/2016

NCI-MATCH Tumor Gene Testing

1010/20/2016

NCI-MATCH Enrollment Expectations

Expected match rate

= one in every four

to five patients

(23%)

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

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

1310/20/2016

NCI-MATCH Step-by-Step Diagram

1410/20/2016

NCI-MATCH Wait Times for Patients

Processing StepMedian

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

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

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

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

1810/20/2016

NCI-MATCH Participation from 1K+ US Sites

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

0000No dataNo data

Arm ID - Drug(s) - Target Abnormality Predicted Prevalence Based on Rates Found in Interim Analysis

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 20Z1B CCND1 amp 3.6 79 H BRAF V600 0.8 19W FGFR1/2/3 2.9 65 T SMO/PTCH1 0.6 14P PTEN loss 2.5 55 R BRAF non V600 0.3 8Q ERBB2 amp 1.7 44 E EGFR T790M 0.2 4S1 NF1 mut 1.9 41 F ALK transloc 0.2 4Z1C CDK4/6 amp 1.7 38 V cKIT mut 0.2 3Y AKT1 mut 1.2 28 A EGFR mut 0 0Z1A NRAS mut 1.2 28 G ROS1 transloc 0 0U NF2 loss 1.1 26 S2 GNAQ/GNA11 0 0N PTEN mut 1.1 24 C2 MET ex 14 sk No Data Not KnownC1 MET amp 0.9 21 Z1D dMMR No Data Not Known

Expected Overall Match Rate = 23%

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

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 date2. 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

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

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

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 13.8Breast 222 13.0Non-Small Cell Lung 127 7.4Prostate 40 2.3

Common Cancers Subtotal 625 36.5

Ovarian 178 10.4Pancreas (Adeno/NOS) 100 5.8Head and Neck 78 4.5Endometrial/Uterine (Non-Sarcoma) 68 3.9Esophageal/GE Junction/Gastric 58 3.4Neuroendocrine 50 2.9Cholangio 47 2.7Bladder/Urinary Tract 40 2.3Endometrial/Uterine Sarcoma 43 2.5Small Cell Lung 32 1.8Other 333 19.5Primary Site Not Specified 53 3.1

Uncommon Cancers Subtotal 1,077 63.5

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

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

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

Thank you for your attention.I welcome your questions!

Question & Answer:

SNAP A #STRONGARMSELFIEBayer 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!)

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, 20162:00ET/1:00CT/11:00PT