SU2C Catalyst^®

DNA Repair Therapies for Ovarian Cancer
This study builds on the groundbreaking work of the SU2C-OCRFA-NOCC Ovarian Cancer Dream Team aimed at developing a standard of care for patients with advanced or metastatic triple negative breast cancer and patients with platinum-resistant recurrent ovarian cancer. The researchers plan to identify key cellular components that drive this recurrent disease to better predict and improve patient outcomes.

Team Leaders:
Alan D’Andrea, MD, Dana-Farber Cancer Institute
Elizabeth M. Swisher, MD, University of Washington

Team Members:
Fleming, Gini F., MD, The University of Chicago
Kaufmann, Scott H., MD, PhD, Mayo Clinic Rochester
Konstantinopoulous, Panos, MD, PhD, Partners in Healthcare

Patient Advocates: Jamie Crase, Kathleen Gavin, Deb Polinsky

Pembrolizumab and Radiation Therapy to Improve Outcome in High-Risk Sarcoma
This innovative combination of immunotherapy (pembrolizumab), and radiotherapy will be assessed for its role in preventing metastatic sarcoma. This project has the potential to change the standard of care and improve survival for sarcoma patients. Crucial insights gained from the translational research associated with the clinical trial will be pivotal for understanding the role of immunotherapy and radiotherapy combination in sarcoma treatment, and pave the way future clinical trials.

Team Leader:
David G. Kirsch, MD, PhD, Duke University Medical School

Team Members:
Ballman, Karla, PhD, Weill Cornell Medical College
Brigman, Brian, MD, PhD, Duke University Medical Center
Demetri, George, MD, Dana-Farber Cancer Institute
Eward, William, MD, University Medical Center
Kozlowski, Erin, BS, MSA, Sarcoma Alliance for Research Through Collaboration (SARC)
Moding, Everett, MD, PhD, Stanford University
Mowery, Yvonne M., MD, PhD, Duke University Medical Center
Riedel, Richard, MD, Duke University Medical Center
Schuetze, Scott, MD, PhD, University of Michigan
Tap, William, MD, Memorial Sloan Kettering Cancer Center
van de Rijn, Matt, MD, Stanford University
Wagner, Andrew, MD, PhD, Dana-Farber Cancer Institute
Weinhold, Kent, PhD, Duke University Medical Center
Young, Steven, BA, Sarcoma Alliance for Research Through Collaboration (SARC)

Patient Advocate: Corrie Painter, PhD, Broad Institute

Targeting Vitamin D Receptors to Make Pancreatic Cancer Competent for Immunotherapy
While current treatment regimens for advanced pancreatic cancer can achieve remission in a majority of patients, the cancer often grows back. A relatively nontoxic therapy is needed to keep the cancer in remission. This proposal tests a combination of immunotherapy (pembrolizumab) and vitamin D analog (paricalcitol) for the maintenance of patients with advanced pancreatic cancer who have been put in to remission.

Team Leader:
Daniel D. Von Hoff, MD, The Translational Genomics Research Institute (TGen)

Team Members:
Barrett, Michael, PhD, Mayo Clinic Arizona
Borazanci, Erkut, MD, Honor Health Research Institute
Chung, Vincent, MD, City of Hope
Downes, Michael, PhD, Salk Institute for Biological Studies
Evans, Ronald, PhD, Salk Institute for Biological Studies
Han, Haiyong, PhD, The Translational Genomics Research Institute
Korn, Ronald, MD, PhD, Imaging Endpoints Research & Core Lab
Liang, Winnie, PhD, The Translational Genomics Research Institute (TGen)
Lowy, Andrew M., MD, University of California, San Diego
Patel, Hitendra, MD, UCSD Moores Cancer Center
Pearson, Talima, PhD, The Translational Genomics Research Institute (TGen)
Truitt, Morgan, PhD, Salk Research Institute

Patient Advocates: Roger Magowitz, Howard Young

Combined Epigenetic and Immunotherapy for Advanced Non-Small Cell Lung Cancer
This ambitious clinical trial combines two epigenetic drugs that reshape DNA with an immune-based therapy for patients with advanced non-small cell lung cancer (NSCLC). Data from this study will identify how modifications to the structure of DNA can make the tumor susceptible to immunotherapies, producing more potent treatments for NSCLC patients. In addition, the team will look for cellular markers that predict who will benefit most from this treatment.  If successful, these results will not only benefit patients with NSCLC but potentially those with other cancer types.

Team Leader:
Stephen B. Baylin, MD, Johns Hopkins University

Team Members:
Borghaei, Hossein, DO, MS, Fox Chase Cancer Center
Brahmer, Julie R., MD, John Hopkins University
Hellmann, Matthew P., MD, Memorial Sloan Kettering Cancer Center
Jewell, Scott, PhD, Van Andel Research Institute
Jones, Peter A., PhD, DSc, Van Andel Research Institute
Marrone, Kristen A., MD, Johns Hopkins
Shen, Hui PhD, Van Andel Research Institute
Wherry, John E. PhD, University of Pennsylvania

Patient Advocate: Beth Flory

Reversing Primary Anti-PD-1 Resistance with Ipilimumab and Nivolumab – Melanoma
This study aims to improve outcomes for patients that have developed resistance to PD-1 immunotherapy. The project adds another checkpoint blockade drug either as a single agent or in combination with PD-1 therapy for metastatic melanoma patients. Associated translational research will provide a molecular understanding to further the clinical development of this combination as well as on how patients respond to single agent or combination therapy in other cancers.

Team Leader:
Antoni Ribas, MD, PhD, University of California, Los Angeles

Team Members:
Byrd, Kenneth, MD, University of Tennessee Health Science Center
Grossman, Kenneth, MD, PhD, H. Lee Moffitt Cancer Center & Research Institute
Hu-Lieskovan, Siwen, MD, PhD, University of California, Los Angeles
Sosman, Jeffrey A., MD, Northwestern University
Ari M. Vanderwalde, MD, University of Tennessee College of Medicine

Patient Advocates: Samantha Guild, Joan Tashbar

Immunotherapy to Prevent Progression in Multiple Myeloma
This project will use immunotherapy to attempt to improve the treatment of simmering multiple myeloma by targeting cells outside the original tumor that are in danger of becoming tumor cells. The clinical trial will attempt to delay organ damage, improve the response to treatment, and maintain remission of the cancer, perhaps even eradicating the early cancer cells as well.

Team Leader:
Irene M. Ghobrial, MD, Dana-Farber Cancer Institute

Team Members:
Adalsteinsson, Viktor A., PhD, Broad Institute
Getz, Gad, PhD, Broad Institute
Manier, Salomon, MD, Dana-Farber Cancer Institute
Park, Jihye, PhD, Dana-Farber Cancer Institute
Shen, Yujia , PhD, Dana-Farber Cancer Institute
Van Allen, Eliezer, MD, Dana-Farber Cancer Institute

Patient Advocate: Jenny Ahlstrom

Tumor Infiltrating Lymphocyte Adoptive T Cell Therapy for Non-Small Cell Lung Cancer
Adoptive T cell therapy trains a patient’s own immune system to attack the cancer, and has been effective in melanoma and some blood cancers. This project will use a novel approach, combining adoptive T cell therapy with immunotherapy for non-small cell lung cancer patients to deliver a one-two punch to tumors.

Team Leaders:
Haura, Eric B., MD, H. Lee Moffitt Cancer Center & Research Institute
Scott J. Antonia, MD, PhD, Duke University

Team Members:
Chen, Dung-Tsa, PhD, H. Lee Moffitt Cancer Center & Research Institute
Creelan, Benjamin C., MD, H. Lee Moffitt Cancer Center & Research Institute
Kaye, Frederic J., MD, University of Florida
Koomen, John M., PhD, H. Lee Moffitt Cancer Center & Research Institute
Jamie Teer, PhD, H. Lee Moffitt Cancer Center & Research Institute

Patient Advocates: Rosalynne I. Miller, Joan Tashbar

Overcoming Atezolizumab Resistance with Epigenetic Therapy in Urothelial Cancer
Cancers can be resistant to particular treatments, or develop resistance over time. This study will attempt to reverse resistance to an immunotherapy using epigenetic therapy in patients with bladder cancer. The epigenetic therapy attempts to “reset” the state of the cancer cells so that they remain susceptible to the immunotherapy. Results could impact treatment of many cancers that are resistant to immunotherapy, as the techniques of using epigenetic treatment to sensitize cells for immunotherapy may be similar across cancer types.

Team Leader:
Peter A. Jones, PhD, DSc, Van Andel Research Institute

Team Members:
Baylin, Stephen, MD, Van Andel Research Institute
Hahn, Noah, MD, Johns Hopkins University
Jewell, Scott, PhD, Van Andel Research Institute
Plimack, Elizabeth, MD, Fox Chase Cancer Center
Quinn, David, MD, USC Norris Comprehensive Cancer Center
Shen, Hui, PhD, Van Andel Research Institute
Issa, Jean-Pierre, MD, Coriell Institute for Medical Research

Patient Advocate: Rick Bangs

Immunotherapy Combination Strategies in ER-positive Metastatic Breast Cancer
Some tumors have ways of blocking themselves off from immune cells. This study examines ways of changing the tumor and surrounding tissues to allow the patient’s own immune cells to attack the cancer. If successful, this would turn non-responsive tumors like ER+ breast cancer into tumors that are susceptible to immunotherapy, opening up new treatment options for many patients this and other solid tumor cancers.

Team Leader:
Ingrid A. Mayer, MD, Vanderbilt University Medical Center

Team Members:
Balko, Justin, PharmD, PhD, Vanderbilt University
Gradishar, William, MD, Northwestern University
Rugo, Hope, MD, University of California, San Francisco
Sanders, Melinda, MD, Vanderbilt University
Shyr, Yu, PhD, Vanderbilt University
Sosman, Jeffrey A., MD, Northwestern University

Patient Advocate:Linda Horton

Neoadjuvant Therapy for Patients with High-Risk Stage III Melanoma

The SU2C Catalyst study will test two different combinations of targeted therapies and immunotherapy to reduce melanoma recurrence risk and improve patient outcomes. This study will utilize neoadjuvant therapy, an approach used to shrink a tumor before surgery. This type of therapy approach is not yet common practice for stage III melanoma but is already routinely used for other types of stage III cancers.

Team Leaders:
Matthew S. Block, MD, PhD, Mayo Clinic, MD, Mayo Clinic, Rochester
Tina J. Hieken, MD, Mayo Clinic, Rochester

Team Members:
Domingo-Musibay, Evidio, MD, University of Minnesota
Flotte, Thomas, MD, Mayo Clinic
Holtan, Shernan, MD, University of Minnesota
Suman, Vera, PhD, Mayo Clinic

Patient Advocate: Cynthia Chauhan, Heidi Turner, Simone Veum

Combination of Ipatasertib and Atezolizumab To Prevent Recurrence In Triple-negative Breast Cancer

The team’s goal is to prevent recurrence of triple-negative breast cancer (TNBC), which is a disease in which the cancerous cells have tested negative for three receptors: hormone epidermal growth factor receptor 2 (HER-2), estrogen receptor (ER), and progesterone receptor (PR). The lack of receptors in the cancer cells means that the hormone therapy and certain drugs that target the receptors are ineffective in treating the disease.

TNBC is very aggressive and prone to spread from the breast after initial treatment with chemotherapy, surgery, and, when indicated, radiation, leading to metastatic disease for which no cure has been developed.  The team plans to use blood analysis (“liquid biopsy”) to detect micrometastatic disease before it can take hold in distant organs and treat it with a combination of drugs.

The team will test a combination of ipatasertib, an investigational drug that blocks a component of the PI3K/AKT cellular signaling pathway, preventing proliferation of the cancerous cells, and atezolizumab (Tecentriq) from Roche, Genentech’s parent company, which is a monoclonal antibody that can “release the brakes” on the body’s immune system and restore T-cell activity that can destroy cancer cells.

Team Leader:
Elizabeth A. Mittendorf, MD, PhD, Dana-Farber Cancer Institute

Team Members:
Carpenter, Erica, PhD, MBA, University of Pennsylvania
DeMichele, Angela, MD, University of Pennsylvania
Keenan, Tanya, MD, Dana-Farber Institute
Mayer, Ingrid, MD, Vanderbilt University Medical Center
McArthur, Heather, MD, PhD, Cedars-Sinai Medical Center
Nanda, Rita, MD, University of Chicago
Park, Beh Ho, MD, PhD, Vanderbilt University Medical Center
Rugo, Hope, MD, University of California, San Francisco
Tolaney, Sara, MD, PhD, Dana-Farber Cancer Institute

Patient Advocates: Elizabeth Frank, Caroline Abi-Khattar

Atezolizumab, Abiraterone, and SBRT in Hormone Sensitive Prostate Cancer

The team is seeking to improve therapy for men with metastatic hormone-sensitive prostate cancer, which is now usually treated with hormone therapy; however, this treatment in most cases only delays progression in what is often a fatal disease.

The team will conduct a clinical trial of a new, three-pronged treatment including:

• Hormone therapy with the drugs leuprolide and abiraterone acetate to reduce the patient’s production of testosterone, which feeds the cancer.
• Stereotactic body radiation, which uses high doses of radiation very precisely targeted to the tumor, over a relatively short period of time compared with standard radiation therapy.
• Atezolizumab (Tecentriq), an immunotherapy drug that allows the body’s immune system to attack the cancer.

Team Leader:
Sean McBride, MD, Memorial Sloan Kettering Cancer Center

Team Members:
Hawley, Jessica, MD, Columbia University Medical Center
Rathkopf, Dana, MD, Memorial Sloan Kettering Cancer Center

Patient Advocates: Jan Manarite, Joel Nowak

Identification of Combination Therapeutics Using JZP-815 for the Treatment of NSCLC

In order to identify more effective treatment options for patients with KRAS-mutant NSCLC, this proposal seeks to use a functional genomics approach to identify therapeutic agents that cooperate with the pan-RAF inhibitor JZP-815 and to evaluate the therapeutic potential of these combinations in clinically relevant mouse models of KRAS-mutant NSCLC.

Team Leader:
Fred R. Hirsch, MD, PhD, Icahn School of Medicine at Mount Sinai

Team Co-leader:
Kwok-Kin Wong, MD, PhD, New York University, Grossman School of Medicine

Principal:
Benjamin Hopkins, PhD, Icahn School of Medicine at Mount Sinai

The LiFFT Study (Lurbinectedin in FET-Fusion Tumors)

The goal of the proposed study is to translate lurbinectedin to the clinic as an EWS-FLI1 targeted agent for patients with Ewing sarcoma. In addition, the Team seeks to determine if the compound is a targeted agent for any of the more than 18-tumors characterized by EWSR1 fusion proteins. Their hypothesis is that lurbinected in will be highly effective in Ewing sarcoma because it will inhibit the Achilles heel of the tumor, EWS-FLI1. If successful, this will lead to an exciting new agent for the treatment of Ewing sarcoma. In addition, it may yield an active compound for the 18 additional tumors characterized by EWSR1 translocation.

Team Leader:
Patrick Grohar, MD, PhD, Children’s Hospital of Philadelphia

Team Co-leader:
Robert Maki, MD, PhD, University of Pennsylvania

Principal
Brian D. Compton, MD, Dana-Farber Cancer Institute

Project Managers
Jennifer Baldi, Children’s Hospital of Philadelphia
Cecilia Carlowicz, CCRC, Children’s Hospital of Philadelphia

Technology-Enabled Immunotherapy Monitoring in NYC Minority NSCLC Patients 

The Team will deploy a mobile health intervention application, ApricityRxTM and the technology-enabled supportive care services, for monitoring and management of immunotherapy toxicities in patients with lung cancer. The key objective of this study will be to evaluate the impact of a contextually tailored tech-enabled remote monitoring framework on the quality of oncologic care in underserved minority patients with lung cancer.

Team Leader:
Vamsidhar Velcheti, MD, New York University Grossman School of Medicine

Team Co-leader:
Rajwanth Veluswamy, MD, Icahn School of Medicine at Mount Sinai

Principals:
Balazs Halmos, MD, MS, Albert Einstein College of Medicine
Brian Henick, MD, Columbia University

Project Manager:
Kristen Labbe, MPH, New York University Grossman School of Medicine

Patient Advocates:
Sulaiha Mastan
Catherine Paykin, New York University Grossman School of Medicine

Targeting Adaptive and Acquired Resistance to Direct KRAS Inhibition

This Team plans to better understand and overcome challenges that limit effectiveness of KRAS inhibitors. First, the team will aim to understand why some patients do not respond to KRAS inhibitors and will develop strategies to increase the number of patients who benefit from therapy. Second, the team will study tumor biopsies and circulating tumor DNA to determine why some patients only respond to therapy for a short period of time before developing resistance to therapy. Based on initial data, the team is also proposing an innovative clinical trial combining a KRAS_G12C inhibitor with an inhibitor of ERK, one of the most downstream mediators of the KRAS pathway, which the team hypothesizes will overcome both initial and acquired resistance to provide durable benefit to patients. Finally, the team will perform single cell sequencing of patient tumor biopsies and use novel mouse models with intact immune systems to understand how direct KRAS inhibition may potentiate the tumor immune response with the goal of rationally designing combinations of KRAS inhibitors and immunotherapy to drive longer lasting responses. Overall, the team anticipates that the proposed research will lead to new and improved therapeutic strategies for patients with KRAS mutated tumors.

Team Leader:
Ryan B. Corcoran, MD, PhD, Massachusetts General Hospital

Team Co-leader:
Scott Kopetz, MD, PhD, The University of Texas MD Anderson Cancer Center

Principals:
Rebecca Heist, MD, Massachusetts General Hospital
David Hong, MD, The University of Texas MD Anderson Cancer Center
Pasi A. Jänne, MD, PhD, Harvard Medical School and Dana-Farber Cancer Institute

Project Managers:
Jennifer Baldi, Children’s Hospital of Philadelphia
Cecilia Carlowicz, CCRC, Children’s Hospital of Philadelphia

Patient Advocates:
Bonnie Addario, GO2 Foundation for Lung Cancer
Anjee Davis, Fight CRC
Manju George, Colontown