The Pancreatic Cancer Collective, the strategic partnership of Lustgarten Foundation, and Stand Up to Cancer (SU2C) awarded additional funding of up to $16 million to four teams of top researchers as part of its “New Therapies Challenge Grants” reported the American Association for Cancer Research (AACR)—a SU2C partner.
The first round of funding, in November 2018, involved $1 million each to pursue preclinical work over 13 months, including several projects seeking to repurpose drugs approved for other uses for their potential to treat pancreatic cancer. Demonstrating promising results enabled them to conduct clinical trials. Chair of the SU2C Scientific Advisory Committee Phillip A. Sharp, Ph.D., the Nobel laureate and MIT scientist, reports: “These are important new investigations that have the potential to save lives with new approaches to therapy.”
Each team will receive up to $4 million over a three-year term for the studies focused on clinical trials. David A Tuveson, MD, Ph.D., chief scientist of the Lustgarten Foundation and director of the cancer center at Cold Spring Harbor Laboratory in New York, reports, “We are impressed by the results of the first round.” He continued, “Under this phased ‘Challenge Grant’ approach, teams are accelerating preclinical work, and we are eager to take the next step to bring new applications for pancreatic treatment to clinical studies.” The AACR will support the administration of the projects receiving funding for the second round.
The research projects include the following:
Targeting SHP2 in Pancreatic Cancer—Team leader: Rene Bernards, Ph.D., Netherlands Cancer Institute; co-leaders: Hana Algül, MD, Ph.D., Technical University of Munich, and Emile E. Voest, MD, Ph.D., Netherlands Cancer Institute. The team focuses on pancreatic tumors that have a mutation in the KRAS gene and has conducted preclinical testing of drug combinations that inhibit specific proteins in the malignant cells. In the second stage, the team will move into a phase I/Ib clinical trial to test the combination of SHP2 inhibitors (RMC4630) and ERK inhibitors (LY3214996). The results are expected to lay the basis for a phase II clinical trial.
Exploiting DNA Repair Gene Mutations in Pancreatic Cancer—Team leader: Alan D’Andrea, MD, Dana-Farber Cancer Institute; co-leader: James Cleary, MD, Ph.D., Dana-Farber Cancer Institute. The team has been seeking to evaluate DNA repair inhibitors and improve the use of PARP inhibitors, which interfere with the ability of cancerous cells to increase in number. The team’s preclinical data suggest that combining gemcitabine with inhibitors that target regulatory proteins involved in DNA repair could be an effective therapy in platinum-resistant pancreatic cancer. Based on these laboratory findings, the team is developing three pancreatic cancer clinical trials testing gemcitabine-based combinations: gemcitabine/ATR inhibitor BAY1895344, gemcitabine/CHK1 inhibitor LY2880070, and gemcitabine/WEE1 inhibitor AZD1775. The most promising combinations will be identified for potential validation in larger trials.
Immunotherapy Targeting Mutant KRAS (mKRAS)—Leader: Robert H. Vonderheide, MD, DPhil, Abramson Cancer Center at the University of Pennsylvania; co-leaders: Elizabeth M. Jaffee, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and Beatriz Carreno, Ph.D., Abramson Cancer Center at the University of Pennsylvania. The team is developing an immunological approach to target mutations in the molecule KRAS, an underlying cause of most cases of pancreatic cancer. In the first round of funding, the team used innovative strategies in bioinformatics, biochemistry, and cell biology to identify specific mKRAS protein sequences that can be recognized by T cells. They then isolated a series of molecular receptors that enable T cells to home in on cancer cells expressing mKRAS. Based on these findings, the team is conducting two different clinical trials with novel vaccines aimed at triggering mKRAS immune responses in patients with resected pancreatic cancer. In round two of funding, the team plans to use the most promising T-cell receptor identified and conduct a clinical trial of engineered T-cell therapy for patients with metastatic pancreatic cancer.
Molecularly Targeted Radionuclide Therapy via the Integrin αv?6—Team Leader: Julie Sutcliffe, Ph.D., University of California Davis; co-leader: Richard Bold, MD, University of California Davis. The team has been working to develop a peptide receptor radionuclide therapy (PRRT) that involves homing in on a protein called integrin αvβ6, a cell surface receptor that can be found in pancreatic cancers. The team has synthesized in the laboratory, a pair of related peptide constructs that are tagged with two different radiolabels. One radiolabel facilitates the imaging of pancreatic cancer lesions in patients that can more likely benefit from the PRRT. The other radiolabel can facilitate the killing of pancreatic cancer cells. The team has obtained promising results in the laboratory testing of the peptide constructs. In the second round of funding, the team will conduct a phase 1 first-in-human study to evaluate the feasibility, safety, and efficacy of the two peptide constructs. The study will determine if one construct can detect lesions in patients with locally advanced or metastatic pancreatic cancer, establish the safety and tolerability of the pair, evaluate the maximum tolerated dose of the second construct, and, using preclinical models, establish an optimal dosing regimen.
About the Lustgarten Foundation & SU2C Partnership
The Lustgarten Foundation and SU2C have collaborated closely since 2012, jointly funding more than 400 investigators from nearly 70 leading research centers in the United States and the United Kingdom. These efforts include 18 multi-institutional teams, including Convergence Teams bringing together computational experts with clinical oncologists and cancer interception—research supporting the earliest diagnosis of pancreatic cancer, even before the cancer may have fully formed. These teams have planned, started, or completed nearly 30 clinical trials. The Pancreatic Cancer Collective is building on this momentum to push the boundaries of what can be accomplished even further.
The Pancreatic Cancer Collective is an initiative of the Lustgarten Foundation and Stand Up To Cancer to improve pancreatic cancer patient outcomes. Together, these leading cancer research organizations will attract new collaborators, improve the diagnosis of pancreatic cancer using big data, find new treatments for pancreatic cancer, and support the next generation of pancreatic cancer investigators. Engaging thought leaders, researchers, institutions, and companies, the Collective will innovate and accelerate research on the edge of science.
ABOUT THE LUSTGARTEN FOUNDATION
Lustgarten Foundation is the largest private funder of pancreatic cancer research in the world. Based in Woodbury, N.Y., the Foundation’s mission is to cure pancreatic cancer by funding scientific and clinical research related to the diagnosis, treatment, and prevention of pancreatic cancer; providing research information and clinical support services to patients, caregivers, and individuals at high risk; and increasing public awareness and hope for those dealing with this disease. Since its inception, Lustgarten Foundation has directed $188 million to research. It has assembled the best scientific minds with the hope that one day, a cure can be found. Thanks to separate funding to support administrative expenses, 100 percent of your donation goes directly to pancreatic cancer research.
ABOUT STAND UP TO CANCER
Stand Up to Cancer® (SU2C) raises funds to accelerate the pace of research to get new therapies to patients quickly and save lives now. SU2C, a division of the Entertainment Industry Foundation, a 501(c)(3) charitable organization, was established in 2008 by media and entertainment leaders who utilize these communities’ resources to engage the public in supporting a new, collaborative model of cancer research, to increase awareness about cancer prevention, and to highlight the progress being made in the fight against the disease. As of December 2019, more than 1,600 scientists representing more than 180 institutions are involved in SU2C-funded research projects.
Under the direction of our Scientific Advisory Committee, led by Nobel laureate Phillip A. Sharp, Ph.D., SU2C operates rigorous competitive review processes to identify the best research proposals to recommend for funding, oversee grants administration, and ensure collaboration across research programs.
Current members of the SU2C Council of Founders and Advisors (CFA) include Katie Couric, Sherry Lansing, Kathleen Lobb, Lisa Paulsen, Rusty Robertson, Sue Schwartz, Pamela Oas Williams, and Ellen Ziffren. The late Laura Ziskin and the late Noreen Fraser are also co-founders. Sung Poblete, Ph.D., R.N., serves as SU2C’s CEO. For more information, visit StandUpToCancer.org.