Research Matters

RESEARCH MATTERS 2021

Spring 2021

ADVANCING THE BEST SCIENCE TO TRANSFORM PANCREATIC CANCER INTO A CURABLE DISEASE.

100% of contributions fund pancreatic cancer research.

For patients and families facing a pancreatic cancer diagnosis, time is everything. The Lustgarten Foundation is a catalyst in the field of pancreatic cancer research, transforming pancreatic cancer outcomes, so patients live longer, healthier lives. Lustgarten-funded research is a force for progress in the scientific community, where creative risks yield high rewards in the pursuit of accelerating and expanding treatment options to provide hope and save lives. In 2021, the Lustgarten Foundation will invest $24 million in pancreatic cancer research focused on three pillars: early detection, personalized medicine and new drug development. Projects are prioritized based on need

and impact and focus on programs advancing discoveries to the clinic. Thanks to you, we are accelerating the pace of research, giving patients access to innovative treatments, uncovering scientific breakthroughs and ensuring the best researchers have the funding to pursue the most life-changing discoveries. Most importantly, with your support, we can envision a future where many more patients are not only surviving but thriving. Despite the challenges presented by the pandemic, pancreatic cancer research has advanced and will continue to progress, because of your support.

dedicated research labs are strategically aligned to dra - matically shift the pancreatic cancer research landscape— from diagnosis to treatment to higher survival rates. 5 $200 m has been invested in more than 300 research projects since 1998. More than

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CLINICAL TRIALS: MOVING RESEARCH FROM THE LAB TO THE CLINIC

NEW CLINICAL ACCELERATOR INITIATIVE TRIALS

$5.1 m to fund three new clinical studies Approved

In early 2021, the Foundation approved $5.1 million to fund three new clinical studies. Two studies led by the team at Johns Hopkins will build on work coming from principal investigators Dr. Dung Le and Dr. Lei Zheng exploring the use of vaccines to treat pancreatic cancer. Both newly funded studies will look at novel combinations of vaccines and drugs targeting the immune system to determine if they can overcome pancreatic tumors’ resistance to immune therapies. The two studies expand on clinical data

generated in ongoing clinical trials at Johns Hopkins and will target specific immune barriers identified as part of those studies. One study will enroll metastatic patients, while the other will enroll patients eligible for surgery. The third study, being led by the team at Dana-Farber Cancer Institute, will look to “re-awaken” T cells (an immune system cell) that penetrate the pancreatic tumors but are rendered “exhausted” and ineffective by signals from the tumor. The clinical study will test a

new combination of drugs designed to simultaneously activate the T cells and block the inhibitory signals from the tumor.

DR. ROBERT F. VIZZA LUSTGARTEN CLINICAL ACCELERATOR INITIATIVE (CAI)

The CAI will shorten the time from clinical trial concept to launch and will allow researchers to develop new clinical trials based on the best available science employing cutting-edge biomarkers. These “smarter” clinical trials will generate large volumes of data scientists can use now and in the future. Even if a trial fails, the data will inform these new concepts, improve future clinical trials, and expedite new treatments. The CAI is guided by our prestigious Translational Advisory Group (TAG), under the leadership of Lustgarten’s Chief Medical Advisor, Elizabeth Jaffee, MD. The TAG is identifying and developing the most promising projects.

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CAI CLINICAL TRIALS IN PROGRESS PASS-01 ( P ANCREATIC A DENOCARCINOMA S IGNATURE S TRATIFICATION FOR TREATMENT)

A united team of pioneering pancreatic cancer researchers from the United States and Canada is conducting the PASS-01 trial designed to predict which treatments might work best for individual pancreatic cancer patients based on the molecular traits of their tumors. In December 2020, the phase 2 trial was launched to look more closely at the two standard of care chemotherapy regimens for advanced pancreatic cancer. The goal of the PASS-01 trial is to uncover more about how the two treatments work. Precision medicine for pancreatic cancer patients includes a comprehensive evaluation of the tumor’s genomic profile. But doctors still do not know enough about the distinct types of pancreatic cancer to determine whether either treatment will help an individual patient, and if so, which treatment might work best. The study includes an in-depth analysis of each participant’s tumor

and response to therapy including generating a tumor organoid for each trial participant. An organoid is a revolutionary 3-dimensional cell culture of a patient’s specific tumor, and the scientific centerpiece of this study. Researchers will use the organoid to analyze the tumor’s biology and drug sensitivity and apply this data to determine if organoids can predict the most effective treatment for each patient. If successful, this trial can pave the way for organoids to personalize therapies for metastatic pancreatic cancer patients. The organoid work for the PASS-01 trial is being conducted at the newly opened, state-of-the-art clinical testing facility established based on the work from the dedicated Lustgarten Foundation Pancreatic Cancer Research Laboratory at Cold Spring Harbor Laboratory in New York State.

THERE IS A CRITICAL NEED TO IDENTIFY WAYS THAT MEDICINE CAN BETTER TREAT PANCREATIC CANCERS. WE BELIEVE BY IDENTIFYING AND LEARNING MORE ABOUT BIOMARKERS AND RESISTANCE PATHWAYS IN THE CANCER, WE CAN HELP MAKE THAT HAPPEN. WE CAN GIVE PATIENTS MORE HOPE THAT THEIR CANCERS CAN BE TREATED EFFECTIVELY. ” —Elizabeth Jaffee, MD, Chief Medical Advisor, Lustgarten Foundation

This trial is funded through the Gail V. Coleman and Kenneth M. Bruntel Organoids for Personalized Therapy Grant.

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CLINICAL TRIALS: MOVING RESEARCH FROM THE LAB TO THE CLINIC (CONTINUED)

The Clinical Accelerator Initiative, guided by the Translational Advisory Group (TAG), is building a network of sites to conduct small clinical trials of 10-20 patients each. These trials will dramatically inform research, enabling investigators to quickly determine if patients are responding to specific treatment approaches and why—information that will continually enhance our approach in clinical trials and clinical care.

Translational Advisory Group members represent the following institutions:

A PHASE 2 STUDY OF PLERIXAFOR AND CEMIPLIMAB IN METASTATIC PANCREATIC CANCER Lustgarten-funded researchers are also conducting a phase 2 study of Plerixafor, an immunostimulant, in combination with Cemiplimab, a PD-L1 inhibitor, to determine if this combination will activate a patient’s own tumor-killing T cells to shrink pancreatic tumors. The trial is based on research led by Lustgarten-funded Distinguished Scholar Douglas Fearon, MD.

This trial is funded by the Stephen and Nancy Grand Philanthropic Fund.

I’M VERY HOPEFUL ABOUT THE FUTURE AS WE BEGIN MOVING OUR SCIENCE INTO THE CLINIC. THIS IS THE NEXT STEP IN OUR EFFORTS TO MAKE PANCREATIC CANCER HISTORY AND IT IS ONLY POSSIBLE BECAUSE OF LUSTGARTEN FOUNDATION FUNDING.

” —David Tuveson, MD, PhD,

Chief Scientist, Lustgarten Foundation

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NEW GRANT PROGRAMS: BUILDING MOMENTUM THROUGH NOVEL RESEARCH LUSTGARTEN FOUNDATION-AACR CAREER DEVELOPMENT AWARDS FOR PANCREATIC CANCER RESEARCH IN HONOR OF RUTH BADER GINSBURG AND JOHN ROBERT LEWIS

When pancreatic cancer claimed the lives of Supreme Court Justice Ruth Bader Ginsburg and Congressman John Robert Lewis last year, the world grieved. In honor of their public fight for equality—and privately against pancreatic cancer—we established two three-year, $300,000 career development awards to address the need for greater gender and racial diversity within the pancreatic cancer research community. The inaugural recipients are:

Ruth Bader Ginsburg Award Dannielle Engle, PhD, an assistant professor at the Salk Institute for Biological Studies, will investigate the role of pancreatitis and inflammation in the formation of pancreatic cancer.

John Robert Lewis Award Avery D. Posey, Jr., PhD, an assistant professor in the Perelman School of Medicine at the University of Pennsylvania, will continue his research to

increase immune system efficacy at attacking pancreatic cancer. The program is supported by Bristol Myers Squibb and is administered by the American Association for Cancer Research (AACR).

THERAPEUTICS-FOCUSED RESEARCH PROGRAM This novel program will foster collaboration and enable researchers to identify new therapeutic approaches and/or drug targets. The Lustgarten Foundation created this unique program to develop a robust pipeline of potential treatments. Funded projects address four key areas of pancreatic cancer biology: Discovering how the stroma—the supportive tissue surrounding the pancreatic tumor—may block treatments from reaching the tumor and design therapies to penetrate this barrier. Understanding and discovering how to block the inflammatory signals that can lead to pancreatic cancer and other pancreatic diseases in response to environmental triggers. Determining ways to stop tumor cell growth by blocking the abnormal metabolic pathways used by pancreatic cancer cells. Preventing the spread—or metastasis—of cancer by isolating metastatic triggers in cancer cells and the stroma.

11 Grants Awarded

$12.3 m in funding awarded More than

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EARLIER DETECTION: IDENTIFYING PANCREATIC CANCER BEFORE METASTASIS

DETECTING CANCER EARLY THROUGH A BLOOD TEST

Most pancreatic cancers are detect- ed only after the disease has me- tastasized, making treatment more challenging and allowing only 20% of patients to qualify for surgery. CancerSEEK, a blood test initially developed by Lustgarten-funded re- searcher Dr. Bert Vogelstein and his lab team at Johns Hopkins Kimmel Cancer Center, can detect the early presence of multiple cancers, includ-

ing pancreatic cancer. A study pub- lished in Science (February 28, 2018) found CancerSEEK has a specificity of greater than 99% and a sensitivity of 72% in patients with pancreatic cancer stages 1-3. In 2019, Thrive Earlier Detection Corp., founded to commercialize CancerSEEK, completed a prospective study of 10,000 healthy patients. Results reported in 2020

showed CancerSEEK more than doubled (25% to 52%) the number of cancers discovered in individuals with no prior history of cancer. New technologies are still being developed to improve the test’s accuracy. In 2021, Exact Sciences, a diagnostic company specializing in the detection of early-stage cancers, acquired Thrive.

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EARLIER DETECTION RESEARCH WASN’T ALWAYS MAINSTREAM. THE SEA CHANGE HAS, IN LARGE PART, RESULTED FROM THE RESEARCH THE FOUNDATION HAS SUPPORTED BOTH HERE AT JOHNS HOPKINS AND IN OTHER LABS. WHEN THE FOUNDATION BEGAN SUPPORTING OUR WORK IN 2008, THEY WERE ALMOST ALONE—THERE WAS LITTLE GOVERNMENT FUNDING AVAILABLE AND VIRTUALLY NO INDUSTRIAL INTEREST. “ ” —Bert Vogelstein, MD, Johns Hopkins

USING ARTIFICIAL INTELLIGENCE TO FIND PANCREATIC CANCER EARLIER Another team of Johns Hopkins research- ers led by Elliot Fishman, MD, is harnessing the power of machine learning, or artificial intelligence, to detect tiny, early-stage tumors on C.T. scans. The FELIX program uses data from thousands of scans to teach computers to detect tumors small enough to be missed by even the most experienced radiologists.

PANCREATIC CANCER COLLECTIVE: COLLABORATING FOR PROGRESS

The Pancreatic Cancer Collective, a joint initiative of the Lustgarten Foundation and Stand Up To Cancer, continues to make groundbreaking progress. The Collective is conducting 30 clinical trials led by more than 400 research investigators at 70 institutions. Four projects supported by the Collective’s “New Therapies Challenge” grants have made it through a second round of funding, enabling researchers to take potential treatments into clinical trials. The grants focus on: Exploiting DNA Repair Gene Mutations in Pancreatic Cancer Immunotherapy Targeting Mutant KRAS Molecularly Targeted Radionuclide Therapy via the Interferon AlphaVbeta6 Targeting SHP2 in Pancreatic Cancer

IDENTIFYING AND TESTING PANCREATIC CYSTS

Pancreatic cysts can be common within the general population, and researchers at Johns Hopkins are making incredible progress in evaluating which cysts are likely to develop into pancreatic cancer, so only those patients with pre-cancerous cysts undergo surgical removal. The Comprehen- sive Cyst (CompCyst) test combines clinical, radiological, genetic and protein marker information to classify pancreatic cysts to determine the best course of action— surgery or surveillance. The Lustgarten Laboratory at Johns Hopkins is working to further develop CompCyst into a clinically approved test.

The Collective also awarded two grants for computational approaches using artificial intelligence to mimic human reasoning and identify individuals in the general population who are at high risk for pancreatic cancer.

Our mission is rooted in the belief that research is fundamental, in fact, it is the only way to produce real results. The Lustgarten Foundation is a catalyst in the field of pancreatic cancer research. Lustgarten-funded science has been a driving force in every major advancement in pancreatic cancer research since 1998. We believe time is everything for pancreatic cancer patients and their families. The Foundation funds research where creative risks yield high rewards to accelerate and expand life- saving treatment options. And we believe in the power of community. Lustgarten programs and events provide people affected by pancreatic cancer a voice and a place to create hope, together. The Lustgarten Foundation is the largest private funder of pancreatic cancer research and 100% of all donations fuel the research to advance understanding of this complex, devastating and historically underfunded cancer.

THE LUSTGARTEN FOUNDATION FUNDS THE WORLD’S PREEMINENT PANCREATIC CANCER RESEARCHERS, DRIVING THE PURSUIT OF BOLD AND INNOVATIVE SCIENCE TOWARD EARLIER DETECTION AND BETTER TREATMENTS AND TRANSFORMING PANCREATIC CANCER INTO A CURABLE DISEASE.

For more information and to donate visit www.lustgarten.org or call toll-free 866.789.1000.

100% of donations fund pancreatic cancer research.

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