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
4
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
ab
t
disseminated to 50 sites through the partnership established
ea
Sunbeatables™: A Sun Safety Curriculum for Preschoolers, initially
nb
expanded the reach of its evidence-based curriculum, Ray and the
and t he Su
The Melanoma Moon Shot prevention program successfully
Ray
JEFFREY GERSHENWALD, M.D.; MICHAEL DAVIES, M.D., PH.D.; JENNIFER WARGO, M.D.
les T
M
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-
15, in addition to Washington, D.C.
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. 5
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. 6
7
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
8
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. 9
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
10
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. 11
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
12
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.
13
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
ic st
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
14
Bi
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interfere with and shut down deadly cancer cells.
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is , or r
. Ph . D
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. 15
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.
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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