Clinical Trials with Targeted Agents (additional contributions to previously committed trials: MEK162 & TAK580): The Team Jack Foundation committed $500,000 to this project in December 2017. The support would ensure the rapid completion of accrual to both, MEK162 and TAK580, protocols, as well as support for the critical analysis of tumor material generated by these trials. This includes not just the standard mutation analysis of the tumor material, but also the identification of secondary pathways of tumor activation and analysis of imaging correlates of tumor response. Finally, due to the release of tumor cell DNA into the blood and possibly cerebrospinal fluid, urine and saliva, termed cell-free circulating tumor DNA (ctDNA), researchers have the possibility of detecting cell-free DNA in these fluids in a non-invasive way to diagnose and profile these tumors for the application of future targeted therapies or monitoring of response, giving them the ability to transform the care of these children. Principal Investigators: Karen D. Wright, MD/ Scott Armstrong, MD, PhD, Dana-Farber Cancer Institute MEK162 February 2019 Update: This study originally had an estimate of 75 patients and now the aim is for over 100 patients and the trial has been extended because of a positive response. While the original trial is taking place at Children's Hospital, other participating treatment sites include: top children’s hospitals in Washington, Oregon, Colorado, Texas, Alabama, Georgia, Minnesota, Missouri, Washington DC, New York and Massachusetts. TAK 580 February 2019 Update: Phase 1 recently finished, and phase 2 is starting soon in 18 different consortium sites across the United States, and potentially expanding internationally to Switzerland. There is much excitement about this clinical trial and there is currently a wait list to participate. There are currently 9 patients enrolled with a maximum enrollment of 120 patients. The first 4 additional sites to open will be University of California San Francisco (UCSF), St. Jude Children’s Research Hospital, Ann & Robert H. Lurie Children’s Hospital of Chicago and Children’s National Medical Center in Washington, D.C.

The Team Jack Foundation, in partnership Nebraska State Legislature, has committed to a $3 million project for the development of a pediatric brain tumor program at UNMC’s Fred & Pamela Buffett Cancer Center. Board Chair of the Team Jack Foundation, Andrew Hoffman, testified for LB 110, a legislative bill to appropriate funds for pediatric cancer specialists, at the Nebraska State Legislature's Appropriations Committee Hearing at the 2015 legislative session. Included in the appropriation are funds to support two additional pediatric cancer specialists. The funds appropriated by the legislation will be utilized to leverage additional private funding. The Team Jack Foundation has committed to funding $1.5 million over six years to match these funds. Plans are currently underway in the development of this ground breaking program.

Through the efforts of the Team Jack Foundation, a multi-disciplinary childhood brain tumor clinic is now functioning in Omaha, Nebraska. In 2013, the Team Jack Foundation, in partnership with the Nebraska State Legislature, agreed to co-fund a $3 million project for the development of a pediatric brain tumor program at the University of Nebraska Medical Center. In addition to the initial $3 million program grant, the Team Jack Foundation has pledged an additional $5 million to the Omaha program, a campaign called the POWER5 Pediatric Brain Cancer Initiative. As a continuation of the funding to the Nebraska Pediatric Brain Tumor Program, the Team Jack Foundation launched the POWER5 Pediatric Brain Cancer Initiative in 2018. From this campaign, the Team Jack Foundation will invest $5 million into the Nebraska Pediatric Brain Cancer Program, over ten years, beginning in 2019. These dollars will fund key areas: 1. Laboratory & Clinical Research Funding laboratory research will allow experts to develop new treatments and offer them to patients through clinical trials. In addition, Omaha will be able to host other national clinical trials as well. 2. Pain Management in Cancer Investing in pain management will help develop a national protocol to help all children fighting cancer better manage pain, especially at end of life. The pain management protocol would include music therapy, massage therapy and more. This type of protocol does not exist for children battling cancer at this time. 3. Education The education piece of the POWER5 program will help develop expertise here in Nebraska with existing medical professionals. It will allow current professionals an opportunity to further their education to become an expert in the area of pediatric brain cancer.

The Team Jack Foundation made a $150,000 commitment to fund a research project focused on Diffuse Instrinsic Pontine Gliomas (DIPG) at Memorial Sloan Kettering in New York. DIPG is the deadliest form of pediatric brain cancer with a 0% survival rate five years after diagnosis. Currently, there is no known treatment specifically for DIPG. Dr. Phillips' lab in recent years has created a treatment that works to reverse tumor cells back into normal cells, but has yet to discover a way to get the treatment into the tumor because of the blood brain barrier. This project will focus on a new drug-delivery method through the blood brain barrier. If successful, this method would lead to new treatments for kids with DIPG and possibly other tumor types as well.

In March of 2020, the Team Jack Foundation announced a three-year commitment to fund a Phase 1 Diffuse Intrinsic Pontine Glioma (DIPG) research project at Children's Hospital Orange County, Dana-Farber Cancer Institute and Lurie Children's Hospital of Chicago. DIPG is the deadliest form of pediatric brain cancer with a 0% survival rate five years after diagnosis. Currently, there is no known treatment specifically for DIPG. This study is titled Heat Shock Protein (HSP) Neo-Antigen Vaccine Plus Checkpoint Blockade for Diffuse Intrinsic Pontine Glioma (DIPG). The hypothesis of this study is that off-the-shelf heat shock protein (HSP) vaccines containing peptides specific for neo-antigen profiles found in DIPG in combination with checkpoint blockade will be safe and tolerable. Investigators also hypothesize that treatment with this vaccine will result in a targeted immune response to the tumor and provide therapeutic benefit. The Team Jack funding commitment was the final piece needed to get this project off the ground. Other funders include: Elerding Family Foundation $100,000, We Love Connie Foundation $225,000, RDL Foundation $300,000, for a total of $625,000. Lead Investigators: Ashley S. Plant, MD (Principal Investigor), Pediatric Neuro-Oncology Lurie Children's Hospital of Chicago Susan Chi, MD (Co-Principal Investigator), Pediatric Neuro-Oncology Dana-Farber Cancer Institute