FY16 Moon Shots Annual Report

FISCAL YEAR 2016

MOON SHOTS PROGRAM

Annual Report

THANK YOU. Thank you for believing in our mission to end cancer.

The University of Texas MD Anderson Cancer Center launched our Moon Shots ProgramTM four years ago with a single charge: to save lives. We told the world that we would do this by assembling teams of expert scientists and investing in the technology they need to improve cancer patient care. We would do this by exploiting the cancer knowledge we already have to make gains quickly against these terrible diseases, and by implementing lifesaving prevention programs on a large scale. But first, we would have to break down those barriers that slow scientific progress.

And time and again, you have shown that the biggest hammer to obliterate those barriers is your generous support. Donors like you help us launch new ideas and allow our scientists to explore new, but untested, avenues of investigation.

Your gifts and pledges are financing a medical revolution that gives many cancer patients more time with their families. For example, in lung cancer — which annually kills more people than colon, breast and prostate cancers combined — our moon shots team is defining a new standard of care for treating advanced-stage tumors previously thought inoperable. Through precisely administered therapies, many patients are living without their cancers getting worse for nearly a year, which is three times longer than previously possible. Patients who once had no hope are now getting more time because of a smart combination of anti-cancer drugs, surgery and radiation. This translates to many more months and possibly years of goodnight kisses, dinners with friends, wedding anniversaries, birthday parties and time building memories. These moments are what your generosity delivers.

Your support also bolsters our efforts against breast cancer, a disease that one in eight women will face. We conducted a small clinical trial of newly diagnosed breast cancer patients with the dangerous BRCA mutation. These women were first given a drug that prevents cancer cells from repairing DNA damage, then they received standard of care chemotherapy and surgery. On average, their tumor volumes shrank by an astonishing 78% after only two months of frontline therapy! Just as exciting, the women in the study experienced fewer side effects compared to standard chemotherapy, which allowed them to continue living their normal lives as they battled their cancer.

Within the following pages, you’ll read more about how the Moon Shots ProgramTM is making strides against a variety of cancers. And at the heart of every project, our focus is on our patients, because ending cancer is the only thing that matters.

AGAIN, ON BEHALF OF OUR FACULTY, STAFF, VOLUNTEERS AND, MOST IMPORTANTLY, OUR PATIENTS AND THEIR FAMILIES, THANK YOU.

TABLE OF CONTENTS Cancer Prevention and Control................................................................................ 4 Melanoma Moon Shot................................................................................................ 5 HPV-Related Cancers Moon Shot............................................................................ 6 Breast and Ovarian Cancers Moon Shot............................................................... 8 Lung Cancer Moon Shot...........................................................................................10 B-Cell Lymphoma Moon Shot................................................................................. 11 Chronic Lymphocytic Leukemia (CLL) Moon Shot............................................. 12 Colorectal Cancer Moon Shot................................................................................. 14 Glioblastoma Moon Shot......................................................................................... 15 Multiple Myeloma Moon Shot................................................................................. 16 Myelodysplastic Syndromes (MDS)-Acute Myeloid Leukemia (AML)

Moon Shot........................................................................................................ 17

Pancreatic Cancer Moon Shot................................................................................ 18 Prostate Cancer Moon Shot.................................................................................... 19 Adaptive Patient-Oriented Longitudinal Learning and Optimization (APOLLO)..........................................................................................................20 Adoptive Cell Therapy...............................................................................................22 Cancer Genomics Laboratory.................................................................................24 Center for Co-Clinical Trials......................................................................................25 Immunotherapy..........................................................................................................26 Institute for Applied Cancer Science (IACS).........................................................27 Oncology Research for Biologics and Immunotherapy Translation (ORBIT)..............................................................................................................28 Proteomics...................................................................................................................29 Translational Research Accelerator.......................................................................30

CANCER PREVENTION AND CONTROL JOXEL GARCIA, M.D.; ERNEST HAWK, M.D.; MARK MORENO The cancer prevention and control (CP&C) platform serves to disseminate what we know prevents cancer to individuals and communities outside the walls of MD Anderson. As you will read, the platform collaborates with various moon shot teams to advance policy, educational programs and

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More than 50% of cancer cases are

community-based clinical service delivery so everyone,

preventable by applying knowledge

including the most vulnerable in our society, has a chance

we already have today.

to reduce their risk of cancer.

MELANOMA MOON SHOT

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disseminated to 50 sites through the partnership established

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Sunbeatables™: A Sun Safety Curriculum for Preschoolers, initially

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expanded the reach of its evidence-based curriculum, Ray and the

and t he Su

The Melanoma Moon Shot prevention program successfully

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JEFFREY GERSHENWALD, M.D.; MICHAEL DAVIES, M.D., PH.D.; JENNIFER WARGO, M.D.

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between the Coordinated Approach to Child Health (CATCH) Global Foundation and the CP&C platform. More than 150 preschool sites have implemented this program; this translates into approximately 500 classrooms and more than 8,800 children impacted across 15 states. Additionally, we developed and produced a kindergarten and first grade curriculum toolkit, now available, and trainings for elementary schools are underway.

Through your continued support of our research, our

providing cutting-edge therapies to our patients.

team has completed an initial analysis of compliance

One exciting clinical trial combines a pair of

by indoor tanning facilities with SB329, a law banning

immunotherapies to deliver a one-two punch to

the use of tanning beds in Texas for young people

melanoma. This unique clinical trial, led by Rodabe

under the age of 18. In collaboration with the CP&C

Amaria, M.D., combines adoptive T-cell therapy,

platform and the Office of Governmental Relations,

which expands and energizes a patient’s own T cells,

we are working with advocates at the American

with immune checkpoint blockade, which removes

Cancer Society-Cancer Action Network (ACS-CAN)

the brakes on T cells, unleashing an immune system

in Washington, D.C., and engaging the MD Anderson

assault on cancer cells. The hope is that these two

Cancer Network , Board of Visitors members and

treatments working in tandem can garner better

clinical and research colleagues beyond Texas to

results in the subset of melanoma patients who do

bring lessons learned from our own legislative

not respond to either treatment when used alone.

®

experience to other states hoping to pass similar legislation. In 2016, Massachusetts and Kansas

Due to the development of more effective

adopted tanning bed legislation, bringing the

therapies, the Melanoma Moon Shot has opened

total number of states with such restrictions to

the first clinical trial evaluating neoadjuvant (pre-

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surgical) immunotherapies. Led by Drs. Amaria and Melanoma Moon Shot co-leader Jennifer Wargo,

Alongside the CP&C platform, we developed the

M.D., patients are randomized to either a single

Skin Cancer Prevention Toolkit for Institutions

agent pre-surgical regimen of nivolumab or a pre-

of Higher Learning to address the unmet need

surgical combination therapy of nivolumab and

of reducing ultraviolet radiation exposure in the

ipilimumab. In addition to the delivery of these two

college setting. This toolkit was distributed to

cutting-edge clinical trials, our team is partnering

288 college campuses across the United States.

with the immunotherapy and Cancer Genomics

Our team is evaluating the feasibility of scaling this

Laboratory platforms to perform deep analyses

initiative even further.

of tissues acquired from patients participating in these studies in hopes of identifying mechanisms

In addition to our prevention efforts, we are striving

of response and resistance, further personalizing

to shift the practice of melanoma treatment by

future treatment strategies.

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HPV-RELATED CANCERS MOON SHOT ERICH STURGIS, M.D.; CATHY ENG, M.D.; LOIS RAMONDETTA, M.D.; KATHLEEN SCHMELER, M.D. Nearly all cervical cancers, most mid-throat and

(ECHO) project and directed at providers within Su

anal cancers, and a large proportion of penile,

Clinica, the federally qualified health center with the

vaginal, and vulvar cancers are attributable to

largest regional catchment area in South Texas. Led

oncogenic types of human papillomavirus (HPV).

by Kathleen Schmeler, M.D., associate professor in

We are focused on increasing HPV vaccination rates,

Gynecologic Oncology, the project is part of a larger

improving screening and developing more effective,

strategy to increase health care provider capacity

less toxic therapies.

in the region. The cervical cancer prevention and management initiative expanded

Alongside the CP&C platform, we continued

internationally to Latin America (10 countries)

our collaboration with state, national and

and Africa (Mozambique and Zambia). A

international leaders to increase the rate of

unique feature of our Mozambique initiative is the

HPV vaccination in the U.S. and globally. At

partnership with our sister institutions in Brazil:

the state level, we are working with the Offices

Barretos Cancer Hospital, Albert Einstein Hospital

of Governmental Relations and Health Policy to

and A.C. Camargo Cancer Center. These partners

contribute to the advancement of the Texas HPV

serve as co-leaders for the initiative.

Strategic Plan, designed in part to educate health providers on how to increase HPV vaccination rates

Our team is also seeking novel drugs for HPV-related

in their patients. This is the result of state legislation

disease and, this year, completed drug testing with

in 2015 for which MD Anderson served as the

nearly 900 unique compounds in multiple HPV-

primary resource. We are also developing a medical

positive cell lines. We also completed genomic

school curriculum on HPV for medical students.

sequence analyses for metastatic anal tumors.

Nationally, we are engaged with ACS-CAN to

Patient-derived xenograft (PDX) models, created

support similar strategies in other states. CP&C

when tissue from a patient’s tumor is implanted

platform leadership is engaging national faith-based

into immune-deficient mice, help investigators in

organization leaders to provide advice and explore

their search for new therapies. We generated five

opportunities to communicate shared priorities

HPV-positive PDX models that should help us more

for cancer preventive strategies, including HPV

accurately predict the behavior of HPV-related

vaccination. Ronald DePinho, M.D., president of MD

cancers in humans.

Anderson, visited the Vatican and met with Pope Francis and other Vatican leaders on behalf of the

Our lab is testing vaccine–drug combinations in

HPV-Related Cancers Moon Shot and the CP&C

preclinical studies of mEERL tumors, a surrogate for

platform teams.

head and neck HPV cancers, and has seen significant tumor regression. We also designed constructs for

The South Texas Cervical Cancer Project continued

screening designated blood components for immune

to hold telementoring clinics for health care

cells specific to HPV. Clinical studies are ongoing and

professionals whose primary service area includes

patient enrollment continues in two immunotherapy

approximately 245,000 women. This project is a

studies investigating immune response and vaccine–

telementoring/teleconsulting initiative using the

drug combinations.

Extension for Community Healthcare Outcomes

Nene Kalu, Ph.D., postdoctoral fellow, breaks up a tumor into single cells for cell line establishment.

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Alpa Nick, M.D., assistant professor of Gynecologic Oncology and Reproductive Medicine, uses the Anderson Algorithm to better treat ovarian cancer.

BREAST AND OVARIAN CANCERS MOON SHOT MIEN-CHIE HUNG, PH.D.; GORDON MILLS, M.D., PH.D.; ANIL SOOD, M.D.; DEBU TRIPATHY, M.D.

Over the past three years, the Breast and Ovarian Cancers Moon Shot has been extremely successful in identifying and offering BRCA1 and BRCA2 genetic testing to MD Anderson patients. We are extending universal genetic testing as a standard-of-care practice for high-risk breast and ovarian cancer patients along with their family members.

Furthermore, in partnership with the CP&C platform, we are making rapid progress in scaling up a dissemination pathway for further integration of patients and family outreach initiatives for identification of BRCA1 and BRCA2 mutations.

Additionally, we are pursuing partnerships at the local After her breast cancer diagnosis,

level, seeking to identify and create proactive processes

Nonnie Arriola, left, learned she had

for referring all triple-negative breast cancer (TNBC) and

a BRCA1 mutation. Genetic testing

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high-grade serous ovarian cancer (HGSOC) patients in Texas,

also revealed her mother, Becky Carson,

as well as their at-risk family members, for genetic testing.

and her daughter, Brianna, carry the

We also aim to influence policy at the institution, state and

mutation. With this knowledge, all three

federal levels with respect to increasing accessibility to

now undergo regular cancer screenings.

genetics services for all at-risk patients.

We are working to disseminate a process that is revolutionizing how we treat ovarian cancer, which typically involves a combination of surgery and chemotherapy. The sequence of those events, though, has been an issue for lack of clear indication of which should be done first. A surgical protocol deemed the Anderson Algorithm, developed and implemented at MD Anderson, has provided an answer that dramatically increases the frequency of complete removal of all visible tumors — a milestone strongly tied to improved survival.

Before use of the algorithm, surgeons were typically able to remove all of a patient’s tumor about 25% of the time. Now, that number is approaching 90 percent after two years of data. All patients who are fit for surgery and are suspected to have advanced-stage ovarian cancer undergo a diagnostic laparoscopy. Two surgeons look at seven different tumor environments and the potential to remove all visible cancerous tissue before independently scoring each area on a scale from 0-2. A third surgeon scores the disease if the first two surgeons disagree in their assessment. Patients with cumulative scores under 8 are immediately scheduled for surgery. Those with cumulative scores 8 or above are treated with chemotherapy before their surgery is scheduled.

The results have been so powerful that medical centers across the world are inquiring about this approach after reading the published data.

Faculty at Hospital Israelita Albert Einstein in Sao Paulo, Brazil — an associate

MD Anderson

member of the MD Anderson Cancer Network® — are actually uploading laparoscopy images so MD Anderson faculty can consult on the scoring. Early discussion with physicians associated with the National Health Service in England could lead to even larger scale adoption of the algorithm. A priority of our program is the dissemination of the Anderson Algorithm in breast cancer clinical trials on a local and national scale.

Hospital Israelita Albert Einstein São Paulo, Brazil

To extend a personalized approach to treating breast cancer, we are taking a novel approach of acquiring and analyzing serial biomarker-guided treatments to those patients who are not responding to standard neoadjuvant chemotherapy.

This gene signature-based approach also will benefit our understanding of the next generation of breast trials through assessment of patients’ responses to targeted therapies. We are also expanding these clinical trials to our Houstonarea locations.

Lastly, one dynamic initiative across our active or soon-to-be active 15 clinical trials is the building of PDX models. The PDXs will be used to determine the potential efficacy of follow-on combination drug discovery studies. The project leads, Jinsong Liu, M.D., Ph.D.; Funda Meric-Bernstam, M.D.; and Helen PiwnicaWorms, Ph.D., are developing a library of pre- and post-therapy PDXs from patients treated with chemotherapy, targeted inhibitors and specific inhibitor combinations within our clinical trials to ultimately identify mechanisms of resistance and further enhance the design of novel clinical trials.

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LUNG CANCER MOON SHOT JOHN HEYMACH, M.D.; PH.D., STEPHEN SWISHER, M.D.; JACK ROTH, M.D. The Lung Cancer Moon Shot opened an international

workplaces;

clinical trial focused on detecting lung cancer in heavy

and efforts

smokers using a blood-based test and computed

to establish

tomography (CT) imaging. In the past year, we

tobacco-free

accrued more than 200 patients at MD Anderson

sports facilities in major

and successfully activated the study in eight other

cities across the nation.

institutions across the U.S., including Dartmouth College, MD Anderson Cancer Center at Cooper (New

In a first-of-its-kind agreement, MD Anderson is

Jersey), Stanford University and Cedars-Sinai Medical

partnering with the Houston Independent School

Center. We have also completed agreements to open

District (HISD) to provide access to an evidence-based,

this study in France, Spain, Canada and China next

youth-oriented tobacco prevention and cessation

year. This initiative will continue accruing data

program for all 110,000 HISD middle and high school

worldwide, and we expect to validate a universal

students. A Smoking Prevention Interactive Experience

blood-based test to detect lung cancer within

(ASPIRE) will be made available in English and Spanish

the next three years.

and used in required health and physical education classes across 46 high schools. Tobacco use is the

In early 2016, the inaugural University of Texas (UT)

single largest preventable cause of death in the U.S.

System Eliminate Tobacco Use Summit was held, which served as a springboard for the amplification of End-

Fiscal Year 2016 was a game changer for therapy

Tobacco™ initiatives across the UT System. Two of the

options offered to lung cancer patients with U.S.

three UT campuses that were not tobacco-free

Food and Drug Administration (FDA) approval

have committed to implementing tobacco-free

of seven new targeted and immune therapies.

policies in the upcoming school year, providing a

Immunotherapy is effective in about 20% of non-

tobacco-free environment for more than 33,500

small cell lung cancer patients when used as single

students, staff and faculty. Along with policy, pre-

agent; therefore, Genomic Marker-guided Therapy

vention and cessation efforts round out a comprehen-

Initiative (GEMINI) efforts in the past year focused

sive approach to creating a tobacco-free culture within

on investigating and developing novel preclinical

the UT System. We expect this initiative will serve as a

studies and clinical trials combining immunotherapy

model for other university systems and college cam-

with targeted therapies. In addition, to advance

puses around the country that seek to protect their

understanding regarding mechanisms of treatment

campus communities from the harms of tobacco.

resistance, we developed two assays that allow us to detect and quantify the presence of immune

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We also made progress on three major policy

cells and targetable checkpoint receptors in tumor

initiatives: Tobacco 21 supports state and local

samples collected from lung cancer patients.

legislation to raise the age to purchase tobacco

Finally, we initiated a major project within GEMINI

products to 21, which evidence shows will reduce

to understand the link between clinical, molecular,

the smoking rate by 12 percent. MD Anderson will

genetic and immune system characteristics of

serve as the primary clinical and research resource

early-stage lung cancer patients. We expect to

for legislation expected in the upcoming session of

soon be able to identify specific characteristics

the Texas legislature; a local ordinance campaign,

of patients with lung cancer that will allow

Smoke-Free Ft. Worth, to protect citizens and visitors

clinicians to select those who will most benefit

to the city from exposure to secondhand smoke in all

from targeted and immune therapy.

B-CELL LYMPHOMA MOON SHOT RICHARD CHAMPLIN, M.D.; MICHAEL WANG, M.D. Our clinical trials are employing several new

From this information, we will develop new therapies

strategies, including “window” trials — in which

and strategies to personalize treatment for each

patients are initially treated with targeted agents

patient. For example, we identified “molecular

before receiving standard chemotherapy. These

signatures” that predict and explain resistance

chemotherapy-free “windows” allow us to enhance

to ibrutinib, one of our most effective therapies,

our efforts at the frontline of the cancer continuum,

and found that they potentially validated the

when lymphoma patients are treated for the first

efficacy of an MD Anderson “homegrown” drug

time, and when novel therapies should work best.

that appears able to overcome resistance.

This approach safely provides insights into the unique efficacy of novel agents and drug combinations

Cellular therapies are showing unprecedented

that will reduce the damaging side effects of

successes in our trials and elsewhere. MD Anderson

chemotherapy. We’re seeing well-tolerated

has made unique contributions with T cells modified

outpatient treatments produce responses that

by chimeric antigen receptors (CARs) recognizing

once required inpatient chemotherapy. We

B-cell antigens and with natural killer (NK) cells; we are

also are testing novel agents in PDX models and will

now combining those approaches by making CAR-NK

use the results from these studies to personalize

cells, specially engineered for longer persistence.

treatments for patients enrolled in our EXPLORE trial,

These designer cells are controlled by a “suicide

the world’s first clinical trial for B-cell lymphoma to be

switch,” which suppresses CAR T cells if serious side

based on a PDX mouse model.

effects emerge, or makes them self-destruct if they attack healthy tissue. Other “secret weapons” are

We’re also gathering intelligence on lymphoma by

being developed or tested, especially by our pilot

detecting expression and mutations of genes in patient

projects, to attack key molecular drivers of B-cell

samples — including PDX tumors — on a genome-wide

lymphoma and to use “liquid biopsies”— simple

scale, and using the power of bioinformatics to predict

blood samples — to detect mutations and monitor

responses to targeted therapy and immunotherapy.

responses to treatment.

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CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) MOON SHOT MICHAEL KEATING, M.B., B.S.; WILLIAM PLUNKETT, PH.D.; WILLIAM WIERDA, M.D., PH.D. The CLL Moon Shot continues to lead the

Richter’s syndrome, a rare transformation of CLL

transformation of therapy for CLL patients, actively

into an aggressive lymphoma, most commonly

presiding over or being deeply involved in the

diffuse large B-cell lymphoma. We have also

breakthrough therapies that have made headlines

found expression of certain miRNAs is involved in

in 2015 and 2016:

resistance to therapy in CLL.

• In 2015, venetoclax (ABT-199) received “breakthrough” status by the FDA. • In March 2016, the FDA expanded its approval

Retrospective analyses of patients receiving the former standard-of-care chemoimmunotherapy

of ibrutinib to the frontline setting for CLL based

identified a population of CLL patients who are at

on findings from the RESONATE-2 trial led by Jan

high risk for therapeutic failure and are in need of

Burger, M.D., Ph.D., at MD Anderson.

improved treatment strategies. We are investigating the unique molecular characteristics of the CLL cells

Our genomics project builds upon the discovery

of patients with different risks to better understand

that microRNAs (miRNAs, small regulatory

how these prognostic categories are genetically and

noncoding RNAs) are involved in the pathogenesis

biochemically different.

of all human cancers. They may actually be encoded

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by viruses. Our work has shown that viral miRNAs

Our pilot project investigates the increased risk for

are significant pathogenic players in aggressive

other cancers seen in patients with CLL, compared

CLL and that both cellular and viral miRNAs are

to the general population, examples of which include

differentially expressed in CLL patients who develop

secondary leukemias, melanoma and head and neck

Jan Burger and colleague in lab. Dr. Burger demonstrated the efficacy of ibrutinib in CLL patients.

cancers. We are profiling the genomic traits of other

Our preclinical studies with CD19‑specific CAR

cancers in patients with CLL to evaluate common

NK cells are showing impressive cancer-killing

genomics, as well as comparative genomics between

power in preclinical models. We anticipate

other cancers in patients with CLL and the same

bringing this novel therapy to patients soon. We also

type of other cancer in the non-CLL population.

have developed a system to produce pre-made, “offthe-shelf” CAR T cells and CAR-NK cells that could be

We have recently identified umbilical cord blood-

given to all patients in need, like blood and platelets

derived natural killer (NK) cells are beneficial in

in blood banks. Adding these cells to blood stem cell

restoring the function of the immune system for

transplants could improve patients’ responses and

patients with CLL. As such, we are conducting a

increase the rate of long-term remissions.

clinical trial of expanded cord blood-derived NK cells to demonstrate the anti-leukemia

In a second approach to immunotherapy, several

response. This trial is ideal for our elderly

immune checkpoint inhibitors have shown promise

patients who are not curable with current

in leukemia. Among these are nivolumab, a

therapies and are not candidates for stem cell

monoclonal antibody that inhibits PD-1, an immune

transplantation.

checkpoint protein that functions like an “off switch” to prevent T cells from attacking tumor

We are developing genetically modified (CAR)

cells. Therefore, we are launching a Phase II trial

NK cells that target CD19, a protein found in CLL.

combining nivolumab and ibrutinib. The hope is this

These cells are made available through the adoptive

combination will be particularly potent in treating

cell therapy platform — a key part of the technical

resistant CLL cases and converting ibrutinib partial

infrastructure established to support the moon

responses to complete responses.

shots and other programs.

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COLORECTAL CANCER MOON SHOT SCOTT KOPETZ, M.D.; PH.D., STANLEY HAMILTON, M.D.; ERNEST HAWK, M.D. In one of the Colorectal Moon Shot’s most exciting

through an aggressive funding program in support

projects, blood-based biomarkers are providing

of pilot projects. These projects involve promising

a simple, noninvasive way to detect colon cancer.

young investigators and innovative research efforts

We have identified several circulating biomarkers

with potential to rapidly advance scientific and

— proteins in the blood that potentially identify

translational discovery in colon cancer research.

patients involved in early cellular changes that precede the development of cancer. We have also

Our plans over the coming year are to further

discovered additional markers that will be validated

develop and begin tests in patients with our

to select those with the highest potential for success

noninvasive blood tests for early detection and

in order to test them in large clinical studies.

disease monitoring. We expect to commercialize our blood-based test that uses multiple

To better classify the disease, we also have identified

biomarkers to detect colorectal cancer and

four molecular subtypes of colorectal cancer and are

circulating cell-free DNA that can find minimal

developing methods to identify them in the clinical lab.

residual disease after therapy. Our work will include analyzing biomarkers contained within tumor

In our basic research labs, we are using human

membrane fragments. Our integromics efforts

tumors in preclinical models to study the different

identify the molecular links between pre-cancers and

molecular subtypes. Using this technology, we can

cancers. We are working to develop a clinical method

analyze, in detail, gene mutations that enable colon

for identifying molecular subtypes of pre-cancers

cancer to grow and spread, and we can begin tests

and cancers to use in clinical trials. Finally, we will

to identify more effective drug combinations against

utilize PDX models with different molecular subtypes

each subtype. With a better understanding of the key

to test more effective drug combinations.

molecular subtype genetic mutations, proteins and other integrated biomarkers, we can determine what makes each colon cancer subtype behave differently from others. These “integromic” profiles will give us new targets for therapies to

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Our group is on the cutting edge of immunotherapy, an emerging field in colorectal cancer. In one important study, we are working to improve patient outcomes by using surgery to reduce tumor burden before treating patients with immunotherapy medications. We are developing personalized “vaccines,” using tissue from a patient’s own tumor, that can boost the patient’s immune system to help fight off the disease.

Colorectal Cancer Moon Shot leaders are seeking novel ideas and unique hypothesis-driven research

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MD Anderson investigators Juan Fueyo, M.D., and Candelaria Gomez-Manzano, M.D., altered the virus that causes the common cold to attack brain tumor cells. The modified virus is called Delta-24-RGD.

GLIOBLASTOMA MOON SHOT AMY HEIMBERGER, M.D.; FREDERICK LANG, JR., M.D.; JOHN DE GROOT, M.D. Glioblastoma (GBM) is a highly aggressive

Within our biological therapeutics initiative, we

cancer with a poor prognosis. Only 5 to 10% of

have nearly completed the Phase 1b clinical trial of

the 15,000 patients diagnosed each year with

Delta-24-RGD, a potent virus that specifically targets

glioblastoma survive for five years after diagnosis

GBM for destruction. Over the next few months,

despite aggressive surgery, radiation therapy and

we hope to conclude the trial and begin analyzing

chemotherapy. Glioblastoma ranks highest among

outcomes. Additionally, we have developed two new

all cancers in needing a true “moon shot” approach,

clinical trials utilizing Delta-24-RGD: a Phase II trial of

bringing the full compendium of technological

Delta-24-RGD plus the immune checkpoint inhibitor

platforms, therapeutic approaches, scientists and

pembrolizumab and a trial utilizing bone marrow-

clinical investigators together in a full-blown assault

derived human mesenchymal stem cells (BM-hMSC)

on this cancer. Over the past year, the GBM Moon

as the delivery mechanism of Delta-24-RGD. This

Shot made great progress as we sought to develop

team will also be working closely with the adoptive

and implement novel therapeutic approaches alone

cell therapy platform to develop BM-hMSC loaded with

and in combination.

Delta-24-RGD. We anticipate obtaining final federal and institutional approval in Q2 of 2017 and initiating these

Our team implemented a new immunotherapy clinical

trials soon thereafter.

trial with the goal of educating the patient’s own immune system to attack GBM cells that express

Through the screening of more than 900 compounds,

cytomegalovirus (CMV), which is present on more

we’ve made significant progress in selecting and

than 90% of GBMs. We also began evaluating the

developing therapies for the central nervous system;

immune response and progression-free survival

these novel single and combinatorial agents have

of the 10 patients enrolled in our ongoing immune

great potential to be effective in treating GBM. More

checkpoint therapy clinical trial. Additionally, we

specifically, these efforts have helped us identify,

evaluated the role of STAT3, an important protein

on a molecular basis, which tumors will respond

that plays a pivotal role in immune suppression in

to unique single or combination therapies. Due

patients with GBM. We are now months away

to the variable nature of GBM, identifying effective

from obtaining FDA approval to initiate a human

biomarkers will be groundbreaking for this field. To aid

clinical trial of a novel small molecule inhibitor

these efforts, we began molecularly profiling tumors

that effectively blocks STAT3 activation. Lastly,

from patients with GBM to develop a biomarker “panel”

our team has successfully developed genetically

for prognostic impact on survival. This allows us to

modified T cells that specifically target a variety of

determine the risk of recurrence and aids in developing

tumor-promoting genes in GBM.

biomarker-driven clinical trials.

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MULTIPLE MYELOMA MOON SHOT ROBERT Z. ORLOWSKI, M.D.; PH.D., R. ERIC DAVIS, M.D.; DONALD BERRY, PH.D. The High-Risk Multiple Myeloma Moon Shot

chromosomal region 1q21 and deletion of

focuses on understanding the key factors involved

region 17p, and demonstrated the ability of a

in plasma cell transformation to myeloma. Our

new homegrown anitibody, Hu8F4, to target

prospective observational study follows patients at

and kill myeloma cells in preclinical models.

increased risk to see when and why they progress to symptomatic myeloma. We are hoping to learn

We are using specific immune cells, natural killer

more about the initial stages of myeloma by using

cells, isolated from umbilical cord blood to eliminate

advanced techniques provided by moon shot

myeloma cells before stem cell transplantation.

platforms. The study seeks to develop accurate

Unlike other immune cells obtained from donors, NK

predictors of myeloma so patients at risk can be

cells do not cause a life-threatening immunological

identified and treated at earlier disease stages.

reaction against the patient’s body (graft versus

Thus far, we identified three molecules

host disease), yet they effectively eliminate myeloma

involved in regulation of the immune system

cells. Thus far, we have treated more than 30

that are expressed differently in patients that

myeloma patients without any adverse reactions

progress early compared to those who progress

and established the optimal dose in a Phase I trial.

later or not at all. The two clinical trials will use

More important, in combination with high-dose

new antibody therapies — isatuximab, targeting

chemotherapy, we achieved complete response

one of the markers on myeloma cells (CD38),

— an important predictor of survival — in half of the

and pembrolizumab, targeting an inhibitor of the

myeloma patients, double our historical results.

immune system (PD-1) — to attack the initial stages of myeloma and hopefully either stop or delay the

The initial results from our studies of donor NK cells

progression to life-threatening stages.

are very promising; in the next stage, we plan to modify the NK cells of donors genetically to further

16

Our pilot projects identified key molecular

increase their effectiveness against myeloma cells by

vulnerabilities of myeloma with the two most

incorporating a CAR recognizing SLAMF7, a specific

common high-risk defects, amplification of

cell surface protein on myeloma cells.

MYELODYSPLASTIC SYNDROMES (MDS)-ACUTE MYELOID LEUKEMIA (AML) MOON SHOT GUILLERMO GARCIA-MANERO, M.D.; HAGOP KANTARJIAN, M.D. Over the past year, the MDS-AML Moon Shot has begun analyzing the prodigious amount of molecular data we generated in previous years. Investigators are focusing on the analyses of two exciting areas: methylation data and transcriptomic/proteomic data. This research has led to the identification of several key molecular targets for future preclinical and clinical assessment.

The first and perhaps most promising target is a type of metabolism that AML cells rely upon to survive. The Institute for Applied Cancer Science (IACS) developed IACS-10759, a drug to starve these cells. This also allowed us to begin to understand the very complex effects of hypomethylating agents (HMA) on methylation patterns, which seem to be affected based on the nature of the genomic region involved.

Moreover, the cell lines used to generate these data are already being used by other groups as key resources for understanding the nature of resistance to these drugs. Resistance to these drugs is one of the largest barriers to saving more patients, so overcoming this problem is a major goal of our moon shot.

Using our large patient sample bank in conjunction with the Adaptive Patient-Oriented Longitudinal Learning and Optimization (APOLLO) platform, led by Ignacio Wistuba, M.D., and Andrew Futreal, Ph.D., we have identified a new molecular prognostic classification for MDS. Most importantly, we have identified a potential molecular marker for therapy-related MDS, a growing problem among cancer survivors.

We also have established expertise with multiple preclinical models, which we have used to understand the fundamental nature of MDS pathogenesis and treatment resistance in vivo. These models have revealed a putative “MDS stem cell,� and we have preliminary data that this cell population is unaffected by hypomethylation treatment and eventually leads to relapse. We are currently attempting to identify new therapies that may effectively target these cells.

Zhihong Fang and

Our cellular immunotherapy efforts have been extremely successful

Guillermo Garcia-

and are continuing to accrue patients. This is especially true of our

Manero, M.D., in the lab

efforts using NK cells, which have already generated very promising results in our ongoing Phase I/II trials. We have also seen very high response rates in our trials using antiviral-specific T cells against cytomegalovirus and the BK virus.

17

PANCREATIC CANCER MOON SHOT JASON FLEMING, M.D.; ANIRBAN MAITRA, M.B., B.S.; ROBERT WOLFF, M.D. Currently, few patients (approximately 5%) enter clinical trials nationally; a goal of the Pancreatic Cancer Moon Shot team is to dramatically increase that number to at least 50%. Another issue our lab faces is the challenging and potentially risky nature of tissue biopsies for our patients. Our team seeks to address both these issues through our novel liquid biopsy program, which enables the complete genomic characterization of every patient’s tumor, using only a single vial of blood. We are now in a unique position to “match” patients to the best trial without the need for them to undergo invasive tissue biopsies. We will also follow these patients in real time to determine how the tumor is changing in response to therapy. This personalized program is a paradigm shift for the treatment of pancreatic cancer. We hope to “MD Anderson treats more pancreatic cancer patients by a factor of five times than any other cancer treatment facility in the world.

Our country can and must generate funds for cancer. It will come from generous patients and personal philanthropic interests. If anyone can end cancer, it is MD Anderson.”

- Tom Rushing, MD Anderson Cancer Center Board of Visitors member and eightyear pancreatic cancer survivor

transition our innovative therapeutic platform to the clinic within the next two years.

Our team has initiated the first “personalized immunotherapy” trial that will use peptide vaccines and T cells (immune cells) geared exclusively towards the genetic makeup of each patient’s tumor.

We have already infused our first metastatic patient using such personalized T cells generated by our lab.

The goal of the early detection program of the Pancreatic Cancer Moon Shot is to develop biomarkers and imaging tools for early detection of pancreatic cancer while it is at the pre-diagnostic stage, dramatically shifting the balance of patients towards surgically removable tumors. We have assembled and validated an anchor biomarker panel based on blinded testing in earlystage blood samples. We have also recently developed enhanced image acquisition, processing and state-of-the-art in-house image registration techniques. Thus, we are aiming at a patientspecific method identifying abnormalities in the pancreas.

Finally, our team has also established Houston’s first high-risk pancreatic cancer clinic, where patients at increased risk can be screened and advised. These are individuals who do not have disease, but remain at a lifetime higher risk (e.g., first degree relatives of pancreatic cancer patients). This new clinic has enormous potential to impact the lives of many families touched by this disease.

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PROSTATE CANCER MOON SHOT CHRISTOPHER LOGOTHETIS, M.D.; TIMOTHY THOMPSON, PH.D.; FILIPPO GIANCOTTI, M.D., PH.D. The Prostate Cancer Moon Shot is looking for

There are no effective therapies to treat prostate

biomarkers, or unique characteristics, of different

cancer in its most advanced form — once it has

types and subtypes of the disease so we can predict

spread to the bone and other internal organs. Thus,

which patients need aggressive treatment and which

we are exploiting a recently discovered weakness of

require no treatment at all. Biomarker research

advanced prostate cancer: that the tumor cells need

underpins the primary projects of the Prostate

to continuously repair their DNA as they multiply,

Cancer Moon Shot.

and they make mistakes during this process that are difficult to correct. The project uses certain drug

One project is testing two complementary forms

combinations that prevent the tumor cells from

of anti-androgen therapy for advanced prostate

repairing their DNA, causing them to die.

cancer. Simultaneously, the project is developing new measurements that will identify the

The first “intent-to-cure” clinical trial for prostate

patients who will respond to this specific

cancer, based on clinical and scientific research at

combination therapy — and possibly cure them

MD Anderson, aims to convert periodic hormone

of their disease. The results of this clinical trial

therapy for a subset of patients into a single-episode

may demonstrate the curative potential of these

curative regimen. Researchers have paired two

two agents used together, as well as help physicians

drugs designed to thwart androgen receptor-driven,

to personalize therapy for those patients who will

castration-resistant prostate cancer in the clinical

benefit from this new approach.

trial for a subgroup of prostate cancer patients.

Earlier studies identified a population of patients

About 80% of patients with advanced prostate

with castration-resistant metastatic prostate cancer

cancer have disease that has spread to the bone,

who might achieve a pathological complete

the tumor’s “microenvironment.” Once in the bone,

response with the combination of abiraterone

prostate cancer can survive and grow only by

and enzalutamide. As of August 2016, 200 eligible

becoming dependent upon specific substances

patients were enrolled in the Phase II study. The two

produced by living bone tissue components. Some

drugs target the androgen receptor-testosterone

new agents, such as immunotherapies, can attack

pathway in different ways to reduce levels of the

these substances and prevent them from being

male hormone that fuels most prostate cancers.

produced. When the prostate cancer cells are

They were initially considered rival drugs. Both

deprived of these substances, they die. Another

are approved by the FDA as single agents for

project is developing and testing new agents to

prostate cancer, but cancers eventually resist them.

prevent these substances from “feeding” prostate

Researchers found that the combination of the drugs

cancer cells that reside in the bone.

thwarts the resistance pathways that arise against them singly.

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ADAPTIVE PATIENT-ORIENTED LONGITUDINAL LEARNING AND OPTIMIZATION (APOLLO) “The idea is to have each patient contributing to and benefiting from research.�

- Andy Futreal, Ph.D., co-leader of the Moon Shots Program as well as the APOLLO and translational research accelerator platforms.

20

IGNACIO WISTUBA, M.D.; ANDREW FUTREAL, PH.D. Organizing and aggregating patient data to optimize treatment for every patient The focus of the Adaptive Patient-Oriented Longitudinal Learning and Optimization (APOLLO) platform is the collection of quality research samples from patients, and subsequent analysis and comprehensive profiling of these samples to accelerate discoveries and practice-changing patient outcomes. This involves standardization of processes for patient consenting as well as sample collection, transportation and profiling, and sharing of research data outcomes.

Portions of the platform supporting consistent

storage of specimens was created while principal

sample collection were implemented for leukemia

investigators from each disease site selected a

patients in 2012. This proof-of-concept study for

specific population of patients to target as part of

specimen collection yielded a total of 2,800 new

the APOLLO platform.

patients consenting to participate, which resulted in 7,400 collected samples.

We have worked to identify existing infrastructures within our organization that can be harnessed to

Patients also were being consented and longitudinal

achieve platform goals rather than investing in new

samples collected over time in MD Anderson’s Ben

resources. The two areas identified are specimen

Love/El Paso Corporation Melanoma and Skin Center.

storage and specimen tracking. In partnership with

As of June 2016, MD Anderson had obtained 522

the Institutional Tissue Bank, our group will continue

tissue samples from 377 patients with melanoma,

to ensure samples immediately are transported and

97 of whom had longitudinal collection out of 757

then prepared for storage, or transported to a moon

who were consented.

shot site lab for analysis.

In January 2016, we received final approval from the

For each moon shot site to accurately request and

Institutional Review Board for a universal banking

track patients and biospecimens at every point

consent form to be used by all moon shot disease

required the use of an existing internal system.

site efforts that will target new patients and various

After review of several internal systems, the team

patient cohorts. This protocol began providing the

determined that the Advanced Research Management

vehicle for moon shot teams and other interested

and Data Analysis (ARMADA) web-based system, with

collaborators to use a uniform consent document

some minor additional software development, best

and to generate and store research data in a

suited platform needs. Functionality of particular

centralized, institutional big data platform known

interest to the APOLLO team was the system’s report

as the Translational Research Accelerator.

generating capabilities. Software development on ARMADA began in January 2016 and is expected to be

Working with the department of Pathology,

piloted during the fall of 2016.

a business plan outlining the various phases, processes and structure of the platform was written

APOLLO team members continue to work with staff

and presented to all moon shot teams. This served

at the Ben Love/El Paso Corporation Melanoma

as the platforms’ official introduction to multiple

and Skin Center in consenting and assisting with

collaborators across all moon shots. We discussed

specimen collection and specimen transportation.

participation and identification of specific patient

Efforts are underway to bring APOLLO to several

populations with leaders in each of the disease sites.

additional tumor sites in the near future.

The infrastructure to support the processing and 21

ADOPTIVE CELL THERAPY ELIZABETH SHPALL, M.D.; CASSIAN YEE, M.D. Designing immune cells to recognize and attack cancer A promising form of immunotherapy involves

The ACT platform is not simply a manufacturer of

engineering the patient’s own immune cells, or

clinical-grade T cells and NK cells. It is designed to

those from a healthy donor to recognize and attack

develop and administer next-generation cellular

tumors. The growth and expansion of these cells

therapies that can be used not only at MD Anderson,

in the laboratory for treating patients is known

but across the United States and worldwide.

as adoptive cell therapy (ACT). This approach has been tested in a number of clinical trials, revealing

We plan to continue accruing patients who could

the power of these immune cells, including T cells

benefit from clinical grade T cell and NK cell

and natural killer (NK) cells, to elicit remarkable

therapies for the aforementioned diseases, as well

responses in many patients with advanced cancers.

as to develop and generate next-generation

These cell-based therapies appeal to patients

cellular therapies that will benefit cancer

because, in contrast to conventional cancer

patients globally. For instance, we are accruing

treatments, they have the potential to treat resistant

glioblastoma patients to a study using the patient’s

disease with minimal side effects and can potentially

own (autologous) cytomegalovirus-specific cytotoxic

protect patients long-term from disease recurrence.

T cells. Another protocol in the validation phase will use donor (allogeneic) bone marrow-derived

Scientists at MD Anderson have developed unique

mesenchymal stem cells loaded with the tumor-

and highly innovative approaches that are not

selective oncolytic adenovirus, DNX-2401, for

available elsewhere. Groundbreaking research to

patients with recurrent glioblastoma. We are

engineer T and NK cells to more efficiently find and

advancing additional protocols to leverage the

kill cancer cells are being translated into the clinic

tumor infiltrating lymphocyte process to address

for a wide variety of cancer types, including acute

the unmet treatment needs of patients with

myeloid leukemia (AML), non-Hodgkin lymphoma,

melanoma, for which there is not an approved

chronic lymphocytic leukemia (CLL), multiple

standard therapy. This protocol will include patients

myeloma, melanoma, glioblastoma, colon cancer

with uveal melanoma, a cancer of the eye as well as

and pancreatic cancer. As the infrastructure for

patients with ovarian cancer. We are also genetically

enabling these technologies, the ACT platform

improving umbilical cord blood-derived NK cells

becomes central to the success of multiple moon

to be more efficient at killing tumors expressing

shots and to the overall mission of MD Anderson

the marker CD19, including acute lymphoid

to eliminate cancer. The ACT platform capitalizes

leukemia, non-Hodgkin lymphoma and CLL. Similar

on the critical mass of scientists and clinicians who

approaches are being developed for myeloid

are leading experts in every aspect of this new

cancers and several solid tumors.

treatment approach.

Elizabeth Shpall, M.D., in the cord blood center (top), Elizabeth Shpall, M.D., and Ian McNiece, Ph.D. (bottom)

22

23

CANCER GENOMICS LABORATORY ANDY FUTREAL, PH.D.; KENNA SHAW, PH.D. Understanding the changes in genes to help us develop treatments for everyone Next-generation sequencing has the ability to

Over the past year, more than 1,700 samples have

transform how cancer is diagnosed and treated by

been sequenced across 11 disease sites. The resulting

identifying changes to the genes that control cell

high-quality data then flows into the Translational

function, particularly how cells grow and divide.

Research Accelerator, which was designed to store

Because every person’s cancer is different and

data and allow all researchers at MD Anderson access.

every tumor has its own unique abnormalities at the

This means cancer experts can use data created

genetic level, MD Anderson clinical researchers can

for one type of cancer that might have an

determine whether a patient’s tumor carries clinically

impact on another type of cancer, thus bringing

significant mutations, some of which may make

together many experts trying to close the gaps in

cancers vulnerable to a particular drug or therapy.

understanding. Our lab serves as an essential part of

They do this by analyzing the tumor tissue sequence

the pipeline that ensures data from multiple platforms

and comparing it to the same individual’s normal

are consistent and comparable.

(non-cancer) sequence. The differences between tumor and normal sequences indicate where

Upcoming goals include technology development to

potential targets may lie.

improve efficiency and allow for reliable sequencing of low quantity DNA/RNA samples. In addition, we are

24

The Cancer Genomics Laboratory performs next-

in the process of developing new sequencing panels

generation sequencing for all the moon shots and

that focus on research discovery needs as requested

provides molecular analyses of genomic DNA and

by moon shot investigators. Applications such as

transcriptomics (RNA sequencing), which has a

these are designed to address specific biological

significant impact on the detection, management

and clinical questions necessary to further our

and treatment of cancer.

understanding of cancer and propel new discoveries.

CENTER FOR CO-CLINICAL TRIALS JOSEPH R. MARSZALEK, PH.D. Taking preclinical insight to clinical trials, then returning to the lab to fine-tune treatments Creating a cancer drug requires years of research

This program is on pace to enter preclinical safety

and testing. The goal of the Center for Co-Clinical

studies to enable filing an Investigational New

Trials (CCCT) is to improve the speed of drug

Drug (IND) application with the FDA. We have also

development. Our integrated model aims to translate

demonstrated efficacy and tolerability of an early

scientific discoveries into drugs at a faster rate, and

PRMT1 inhibitor compound in vivo in pancreatic

identify specific patient populations most likely to

ductal adenocarcinoma (PDAC), thus advancing

respond to drugs in safe, effective clinical trials.

the program into lead optimization to improve the pharmaceutical properties of this class of inhibitors.

The CCCT has been essential to advancing the preclinical development of novel inhibitors

In collaboration with the Melanoma and Lung Cancer

developed at MD Anderson, and also to advancing

Moon Shots, we have executed a series of preclinical

compounds that are in clinical evaluation.

trials to inform co-extinction strategies that combine targeted agents with immune-modulating agents.

Collaborating with our moon shots teams, we have

These results are being used to prioritize potential

established robust anti-tumor activity of our

clinical trials. Several other projects to evaluate

novel inhibitor of oxidative phosphorylation,

novel therapeutic strategies, in particular with the

IACS-010759, in relevant preclinical models

Melanoma, Pancreatic and Breast and Ovarian

of MDS-AML, melanoma, pancreatic and

Cancer Moon Shots, are in earlier stages.

colorectal cancers and glioblastoma. In preparation for an upcoming Phase I trial in AML,

Additionally, Boehringer Ingelheim and MD Anderson

which began enrollment in October 2016, we ran

announced a partnership in December 2015

tests that measure target inhibition and that will

focusing on developing innovative medicines for

provide early readouts of drug activity.

pancreatic cancer. The new collaboration combines our unique understanding of potential biological

We have demonstrated anti-tumor effects of our

drivers of the disease with Boehringer Ingelheim’s

lead glutaminase inhibitor compound in preclinical

experience in drug discovery and development.

studies in a biomarker-selected subpopulation

The collaboration will focus on identifying and

of non-small cell lung cancer models. Similar

developing novel inhibitors as well as identifying

studies and results were completed in a molecular

biomarkers that can accurately predict patients

subtype of high-grade serous ovarian carcinoma.

who would respond to potential new therapies.

“We knew we were onto something when we put this molecule into animals and saw tumor regression. Rarely do you see strong regression. If we see the same types of responses we’re seeing in the preclinical models, this will highly impact what we do in the clinic.”

- Dr. Joseph Marszalek on the development of IACS-010759

25

Diagnosed at 19 with ocular melanoma, a rare form of eye cancer, Britta Fortson was cancer-free for 20 years. In 2015, after learning her ocular melanoma had returned and spread to her liver, Britta came to MD Anderson where she is receiving immunotherapy treatment as part of a clinical trial.

IMMUNOTHERAPY JAMES ALLISON, PH.D.; PADMANEE SHARMA, M.D. PH.D.; PATRICK HWU, M.D. Providing the Moon Shots Program with support for immunotherapies in the treatment of a wide variety of disease sites Immune checkpoint targeting is a new paradigm for

biomarkers to identify patients who are likely

cancer treatment. Rather than targeting the tumor

to respond to, or develop adverse reactions to,

cell, this approach targets molecules on immune

therapies. The immunopathology component seeks

cells that regulate their activity to sustain immune

to provide understanding of changes in the tumor

responses to cancer and achieve elimination of

microenvironment associated with therapies.

tumors and immunity to recurrence. This strategy has proven effective in treating many types of cancer

The immunotherapy platform has contributed

and is now the standard of care for metastatic

to projects across 18 departments, and

melanoma. The immunotherapy platform provides

involving 93 clinical trials. We have collected

MD Anderson investigators with support for

and processed more than 38,000 blood and

immunotherapies in the treatment of a wide variety

tissue samples since June 2013. With the

of tumor types and helps to link immunologic data

platform’s expertise, nearly every moon shot is

with the genomic and proteomic platforms.

engaged in exciting immunotherapy programs.

The platform has three components. The preclinical

The infrastructure of scientists and clinical personnel

studies group helps establish feasibility and efficacy

for the immunotherapy platform has more than

of new treatments and combinations in animal

doubled and will continue to expand to support fast-

studies. The immunologic monitoring component

paced collections and analyses. The purchase of new

provides instrumentation and technical support

state-of-the-art equipment and enhanced systems

for cellular and molecular analysis of the impact of

will enable new studies, which will facilitate analyses

therapies on the immune system in order to gain

that will impact clinical outcomes.

insight into mechanisms of action, and to discover

26

INSTITUTE FOR APPLIED CANCER SCIENCE GIULIO DRAETTA, M.D. PH.D.; PHILIP JONES, PH.D. Applying scientific knowledge of tumor development and growth into the creation of cancer therapies When the Institute for Applied Cancer Science

was submitted to the FDA in July 2016 requesting

(IACS) was founded in late 2011, our main objective

permission to initiate clinical testing. Trials in AML

was to advance a therapy into clinical testing within

patients here at MD Anderson will be led by Marina

five years. With IACS-010759 initiating Phase I

Konopleva, M.D., Ph.D., and Naval Daver, M.D. Plans

testing, we have achieved this goal.

to initiate clinical trials in other diseases in early 2017 are ongoing.

We have received formal approval from the FDA to initiate a clinical trial for this leading program, and

Working closely with the Lung and Ovarian Cancer

the first AML patient in this Phase I clinical trial was

Moon Shots, a molecule known as IACS-6274 targeting

treated in Q4 of 2016. This molecule, IACS-010759,

a different metabolic enzyme has been identified

an inhibitor of oxidative phosphorylation, shuts

to advance into toxicology testing with the goal of

down a specific metabolic pathway that certain

initiating clinical testing at the end of 2017. The project

cancer cells depend on for their energy, essentially

focused on a specific protein discovered by CCCT

starving cancer cells of their fuel supply. The IACS

scientists involved in driving progression of pancreatic

and CCCT project teams have demonstrated that

cancer, which has moved ahead significantly this year

AML patients, as well as subsets of lymphoma,

as lead molecules are showing encouraging effects in

brain and pancreatic cancer patients, could benefit

preclinical models of pancreatic cancer.

from this novel agent; plans are afoot to explore these indications in the coming year. In the past 12

Additionally, in early 2016, a drug discovery and

months, the team has conducted the mandatory

development collaboration in immuno-oncology

safety/toxicology studies required by the FDA,

was signed with TESARO, Inc., an oncology-focused

and the clinical supplies have been manufactured

biopharmaceutical company. This will fast-track new

under very strict quality control. An IND application

immune-modulating therapies for cancer patients.

27

ONCOLOGY RESEARCH FOR BIOLOGICS AND IMMUNOTHERAPY TRANSLATION (ORBIT) CARLO TONIATTI, M.D., PH.D.; JEFFREY MOLLDREM, M.D.; MICHAEL CURRAN, PH.D. Accelerating the translation of novel discoveries into therapeutic treatment with monoclonal antibodies There is an urgent need to discover new cancer

one in monotherapy and a second in combination

targets and to develop monoclonal antibodies —

therapy with another immunotherapeutic mAb.

mAbs, “magic bullets” that can be manufactured

Both trials are proceeding as expected, with

to recognize target molecules on the surface of

initial data on potential therapeutic efficacy

cancer cells and attack them. Over the years, our

expected in 2017.

investigators have identified novel targets for antibodies, but it has been difficult to translate these

The second ORBIT program is Hu8F4, a first-in-class

findings into clinical trials. Developing a therapeutic

mAb that has been generated for the treatment

mAb from target identification to clinical trial for

of AML. Hu8F4 selectively kills AML cancer cells

patients is a complex and expensive process.

that express a specific target, PR1/HLA2, on their

Academic researchers often have scarce resources

surfaces. We are now in an advanced stage of the

and limited familiarity with all the steps required to

manufacturing process (i.e., large-scale production

advance discoveries from lab to clinic. The result is

of clinical-grade mAb that will be administered to

a lengthy and inefficient drug development process

patients), and we are generating the data required

and years of delays in the clinical development of

by the FDA to approve a Phase I trial during the first

promising new anti-cancer agents.

half of 2017 in relapsed and refractory AML patients expressing PR1/HLA2.

The goal of ORBIT — the Oncology Research for Biologics and Immunotherapy Translation platform

Both the OX40 and Hu8F4 mAbs have attracted

— is to change that. With our team of drug discovery

the interest of the pharmaceutical industry,

and development experts, we are committed to

traditionally the vehicle for advancing novel agents

accelerating the time required to convert novel

to patients. We have signed research collaboration

discoveries made at MD Anderson into therapeutic

and license agreements with two major international

opportunities for our patients. Offically launched in

pharmaceutical companies.

2014, ORBIT is already delivering on this objective.

Additional programs are at different stages of The first ORBIT program is an OX40-agonist

preclinical development. In the most advanced

immunotherapeutic monoclonal antibody. It is now

programs, we plan to select optimal clinical

in clinical development. Based on the preclinical data

candidates by 2017.

generated at ORBIT, two Phase I trials were started,

28

PROTEOMICS “The platform is helping the MDS-AML Moon Shot understand drug resistance

SAM HANASH, M.D., PH.D. Sifting through thousands of cancer-related proteins to find those useful for cancer care

and identify new targets for these diseases.�

The proteomics platform provides state-of-the-art instruments, specialized expertise and other resources needed to sift through thousands of cancer-related proteins. The goal is to help investigators identify which proteins are useful for advances in diagnostics, imaging or targets for various types of treatments, from immunotherapies to targeted therapies.

We also strive to determine biologically relevant biomarkers — proteins in the blood that potentially identify patients undergoing early cellular

- Moon shot leader Guillermo Garcia-Manero, M.D., professor of Leukemia

changes that precede the development of cancer. These biomarkers can potentially identify sensitivity and resistance to drug treatment and characterize adaptive responses as we pursue the potential of combining drug targets.

This past year, our lead program, a blood-based biomarker to detect lung cancer early, was ushered into clinical trials in the U.S., Europe and China by the Lung Cancer Moon Shot. Our goal is to validate, on a worldwide scale, that a single drop of blood can diagnose lung cancer and thus save patients from intrusive, expensive procedures. This test has the potential to save the worldwide health system billions of dollars and completely change the way lung cancer is diagnosed. The technology crosses over to other cancer types, including breast cancer, pancreatic cancer, colorectal cancer and ovarian cancer.

29

TRANSLATIONAL RESEARCH ACCELERATOR ANDREW FUTREAL, PH.D.; VINOD RAVI, M.D.; CHRIS BELMONT; BRETT SMITH Every patient benefiting from — and contributing to — treatment decisions We continue to make remarkable progress in the

This, in turn, adds to the flexibility of both

development of our translational research accelerator

identification of a population of interest and the

platform (formerly Big Data). We have grown the core

visualization of results pertaining to that population.

team substantially with outside expertise.

The impact of such a tool in supporting hypothesis generation and identification of study populations

We have added several new structured data sources

is immense. Your generous support has made this

while continuing to mine the more challenging yet rich

breakthrough in the research process possible.

clinical data from medical oncology, surgery, radiation and pathology records. This platform is built to

This is a remarkable juncture in the history of cancer

support deep analytics and will support our extension

research and the wealth of data that it produces. The

to MD Anderson Cancer Network partners, providing

challenges ahead include how to best interact with

a national presence once fully implemented.

and integrate external data sources, how to engage

®

with and gather data from our MD Anderson Cancer We are at the point of having ingested all common

Network partners and, most importantly, how to

clinical data elements and research data for 258,000

completely maximize the opportunity presented to

patients, with each new patient being enrolled

us with our move to the new electronic health record

through nightly updates of data fields. We are in the

system. Your support will enable the platform to

process of adding 60,000 new patients from the

integrate new data sources, add new tools, update

electronic health record system since its launch on

current sources and continue to operate efficiently.

March 4, 2016. This represents perhaps one of

30

the most comprehensive efforts ever attempted

The translational research accelerator platform

in the extraction of clinical data from diverse

is crucial to realizing the goal of every patient

electronic health record platforms. Our

contributing to and benefiting from research. We

computational biologists have been helping clinicians,

are now uniquely poised to take advantage of the

physician scientists and basic researchers analyze

big data analytical resources. The clinical and

genomic data and integrate it with clinical data. Our

molecular data we have ingested into the platform

custom-built user interface allows construction of

can be utilized to identify factors that help patients

cohorts with specific selection criteria. Further, we

live longer and live better. These cutting-edge

have standardized analytical outputs powered by

efforts will ensure that patients who entrust their

Tableau, an industry standard query and visualization

care to MD Anderson will be partners in Making

tool, to facilitate the work of investigators.

Cancer History ®.

For more updates, visit: CANCERMOONSHOTS.ORGTM

CANCERMOONSHOTS.ORG