PHASE ONE Medical Grant

PHASE ONE Medical Grant is sponsored by PHASE ONE Foundation. PHASE ONE supports groundbreaking Phase I and II clinical cancer trials, innovative education and treatment programs, and forward-thinking leaders in the scientific and medical community.

Medical Grants — PHASE ONE Foundation Apply for a Medical Grant Apply for a Community Grant PHASE ONE’s mission is to support groundbreaking Phase I + II clinical cancer trials, innovative education and treatment programs, and forward-thinking leaders in the scientific and medical community. Our focus is funding the early steps in the research process as new treatments and therapies are given to patients for the first time.

PHASE ONE has supported over 55 medical grants for innovative cancer clinical trials and treatments. See below for our past grant recipients and keep an eye on our News page for updates. If you are interested in submitting a proposal for a PHASE ONE Medical Grant, please click here for more info.

PHASE ONE Granting Committee with PHASE ONE Grant Recipient Dr. Santosh Kesari of Saint John's Cancer Institute PHASE ONE-funded trials that are currently recruiting and accepting patients 2025 Neuroblastoma, Children's Hospital Los Angeles, Araz Marachelian, MD, MS “Improving Outcomes in High-Risk Neuroblastoma: A Phase II Study of Allogeneic Natural Killer Cells with Chemoimmunotherapy" Neuroblastoma is the most common solid cancer outside the brain in children, and about half of patients are diagnosed with an aggressive, high-risk form.

Even with extremely intensive treatment, only around half of these children survive, and outcomes are especially poor when the cancer returns. One important advance has been dinutuximab, an immunotherapy that targets the GD2 protein on neuroblastoma cells and modestly improves survival. However, many children still relapse because neuroblastoma can shut down the immune response using molecules like TGF-beta.

Dr. Marachelian’s team is testing a new approach that combines dinutuximab with “off-the-shelf” Natural Killer (NK) cells from carefully selected healthy donors whose immune systems are naturally strong at recognizing cancer. In the lab, these donor NK cells are expanded in the presence of TGF-beta so they learn to resist this suppressive signal and become more effective tumor killers.

The cells are then frozen and kept ready for use when a child needs treatment, allowing multiple cycles of therapy without manufacturing delays. In this Phase II clinical trial, children with relapsed neuroblastoma receive standard chemoimmunotherapy plus these enhanced universal donor NK cells. Early participants have tolerated the treatment well and have been able to continue normal activities, including attending school.

The study will enroll 50 patients through the New Approaches to Neuroblastoma Therapy (NANT) Consortium. If successful, this strategy could change how relapsed neuroblastoma is treated by pairing standard therapy with immune cells engineered to resist suppression and keep fighting, with potential implications for other childhood cancers as well.

2025 Glioblastoma, City of Hope, Christine Brown, PhD “Phase I Clinical Trial of TGFβ-Resistant CAR T Therapy for Treatment of Glioblastoma" Glioblastoma is one of the most aggressive and lethal brain cancers, growing quickly, invading healthy tissue, and resisting surgery, radiation, and chemotherapy.

Most patients live only 12–24 months after diagnosis, and fewer than 10 percent survive five years, underscoring the urgent need for new therapies. This Phase I trial tests a next‑generation CAR T cell therapy that reprograms a patient’s own immune cells to recognize and attack glioblastoma.

Building on earlier studies showing that IL13Rα2‑targeted CAR T cells can be safely delivered to the brain and, in some patients, induce dramatic tumor regression, Dr. Christine Brown’s team will use CRISPR‑Cas9 gene editing to create CAR T cells that both target IL13Rα2 and are resistant to TGFβ, a powerful “off switch” that tumors use to shut down immune responses.

Patients with recurrent glioblastoma or related high‑grade gliomas will have their T cells collected, engineered, and expanded in the lab, then delivered directly into the brain through surgically placed catheters in weekly treatments. The trial’s primary goals are to assess safety, identify the optimal dose, and evaluate the feasibility of this complex, locoregional CAR T approach, while also monitoring early signs of clinical benefit.

By supporting this first‑in‑human study of TGFβ‑resistant CAR T cells for glioblastoma, PHASE ONE is helping to advance a bold new strategy for patients who have had very few treatment options.

2025 Kidney Cancer Detection, Saint John’s Cancer Institute, Jennifer Linehan, MD “Cell-free miRs as New Biomarkers for Kidney Cancer" Kidney cancer affects nearly 90,000 people in the United States each year, leading to approximately 18,000 deaths annually.

RCC accounts for approximately 85% of all kidney cancer cases and is known for its aggressive nature and high propensity for metastasis, making early detection and effective monitoring critical. Kidney cancer often advances silently, with patients rarely showing clinical symptoms until the tumor has grown large enough to metastasize.

As a result, many patients learn they have kidney cancer incidentally after undergoing an imaging test like a CT scan or MRI. However, these imaging techniques cannot reliably differentiate between cancerous growths and those that are harmless. Additionally, once kidney cancer is diagnosed, there are no existing blood or urine tests to assess the aggressiveness of the cancer or predict recurrence.

In response to this unmet need, Dr. Linehan and her team at Saint John’s Cancer Institute are pioneering a research initiative to develop tests that leverage microRNAs (cfmiRs) as potential biomarkers. These tiny, yet powerful, molecules can provide vital insights into cancer. Previous studies have shown that these cfmiRs can be detected in both blood and urine, indicating their potential for non-invasive diagnostic approaches.

The proposed study will analyze cfmiRs collected from blood and urine samples from at least 65 patients each year over three years. By comparing the cfmiR profiles in these biofluids to those obtained from cancerous tissue, the research aims to identify unique patterns that can inform clinicians about the presence of RCC, its aggressiveness, and its chances of recurrence.

This method promises to decrease the need for invasive procedures like biopsies, which can be uncomfortable and may not always yield clear insights. Using advanced techniques such as Next-Generation Sequencing (NGS), this research aims to craft a comprehensive diagnostic panel for RCC that integrates these cfmiR analyses.

The anticipated benefits include increased accuracy in diagnosing kidney cancer and developing targeted monitoring strategies that ultimately lead to tailored treatments and enhanced survival rates for patients. This research represents a vital step toward a future where kidney cancer can be detected and monitored more effectively, ultimately improving treatment options and patients' quality of life.

By unlocking new insights into the biology of kidney cancer through the study of cfmiRs, Dr. Linehan aims to make early detection a reality for more patients, creating a significant impact on the future of cancer care.

2024 Hereditary Kidney Cancer, UCLA, Brian Shuch, MD “A Phase I Trial of 6-Mercaptopurine (6MP) for the Treatment of Hereditary Leiomyomatosis and Renal Cell Carcinoma" Dr. Brian Shuch at UCLA is leading a Phase I study to investigate a new treatment for Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC)– a rare genetic condition that leads to kidney cancer and various debilitating symptoms.

HLRCC is the most common hereditary kidney cancer syndrome, affecting approximately 1 in 2,000 individuals. Of those with HLRCC, ~10-16% will develop kidney cancer, highlighting the urgent need for effective treatment options. Current therapies, including immunotherapy and chemotherapy, have shown limited success, often leading to rapid disease progression and reduced survival rates.

Recently, UCLA researchers identified a key vulnerability in HLRCC kidney cancer: it relies on a backup system (the purine salvage pathway) for growth. Fortunately, existing FDA-approved drugs, 6-MP and AZA, can block this pathway. Pre-clinical tests show these drugs effectively kill cancer cells in lab and animal models.

Building on this breakthrough, Dr. Shuch will investigate the use of 6-MP for HLRCC. Since this medication is already FDA-approved, generic, and affordable, repurposing it could fast-track a promising new treatment for patients. If successful, this trial could significantly enhance treatment options for HLRCC– offering new hope to patients and their families.

2024 Rare Head & Neck Cancer, Dana-Farber, Glenn J. Hanna, MD “A Phase I/II Study of CB103 (Oral Pan Notch Inhibitor) With Abemaciclib or Lenvatinib in Combination in Patients With NOTCH Activated Adenoid Cystic Carcinoma (CALCulus)" NOTCH-activated Adenoid Cystic Carcinoma (ACC) is a rare cancer that primarily affects the salivary glands in the head and neck.

ACC has significant treatment challenges due to its rarity, high rates of distant metastasis, and the limited effectiveness of current options for advanced cases. While initially manageable through surgery and radiation, nearly half of ACC patients eventually face metastasis.

Current treatments, including chemotherapy and immunotherapy, have shown limited clinical benefits, underscoring the urgent need for new therapeutic strategies for this difficult-to-treat cancer.

Dr. Hanna’s trial is studying the effects of CB-103, an oral pan-Notch inhibitor, in combination with other therapies for patients with NOTCH pathway mutations—a mutation frequently observed in aggressive ACC cases and associated with shorter relapse-free periods and poorer survival rates.

This is a groundbreaking study that, if successful, could transform treatment approaches and improve survival rates for those affected by NOTCH-activated ACC.

2024 Oral Cancer, GLAVREF, Marilene Wang, MD “APG-157 and Immune Checkpoint Inhibitors for Treatment of Head and Neck Cancer" Oral and oropharyngeal cancers often present at advanced stages, with traditional treatments like surgery, radiation, and chemotherapy leading to significant morbidity and poor outcomes. There is a critical need for safer, more effective treatment options. This study, led by Dr. Marilene B.

Wang, aims to explore a less toxic and more effective treatment for head and neck cancers, particularly in veterans, who are at higher risk due to increased smoking and HPV infection rates. Building on preclinical studies that showed turmeric's strong suppressive effect on head and neck cancers, the Phase II trial will test the efficacy of APG-157, a turmeric pastille.

APG-157 contains the full spectrum of turmeric's active compounds, including curcumin, and is expected to induce tumor cell apoptosis, reducing tumor burden and improving outcomes from local therapies. The trial will assess APG-157’s effectiveness by measuring pathological responses, immune biomarkers in saliva and blood, and changes in tumor tissue in patients with Head and Neck Squamous Cell Carcinoma (HNSCC).

If successful, this study could transform the treatment of oral and oropharyngeal cancers, offering a less toxic therapy that enhances survival rates and quality of life.

2024 Pancreatic Cancer, Cedars-Sinai, Arsen Osipov, MD “Sensitizing Pancreatic Cancer to Immunotherapy” Pancreatic cancer is one of the deadliest and most aggressive forms of cancer and is on track to become the second leading cause of cancer-related mortality within the next decade. While immunotherapy has shown promise in other cancers, pancreatic cancer remains stubbornly resistant.

Dr. Arsen Osipov and his team at Cedars-Sinai are tackling this challenge by investigating how to make pancreatic tumors responsive to immunotherapy. Their focus lies in understanding and altering cellular dynamics within the pancreatic tumor microenvironment (TME), transitioning it from a “cold,” immune cell barren tumor environment into a “hot,” immune abundant one.

Dr. Osipov's team has identified a promising avenue for unlocking the full potential of immunotherapy by blocking a unique protein in the TME, known as C-X-C chemokine receptor 4 ( CXCR4 ). In their Phase I/Ib trial, researchers plan to combine Balixafortide , a best-in-class CXCR4-targeting drug, with a novel FDA-approved immunotherapy, Cosibelimab.

Balixafortide has been extensively studied in Phase I-III trials in multiple other tumor types, particularly breast cancer, and has shown to be safe both alone and in combination with chemotherapy. Combining it with immunotherapy could prove to be a safe and well-tolerated regimen with significant potential of decreasing metastasis and increasing anti-tumor effect.

The study will evaluate the safety and potential efficacy signal of this combination therapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who have experienced disease progression following standard chemotherapy. If successful, this trial could lay the groundwork for future studies exploring multiple treatments targeting various aspects of the TME.

This has the potential to overcome pancreatic cancer's resistance, potentially changing the landscape of its treatment across all stages of the disease and offering a new avenue of hope for all pancreatic cancer patients.

2023 Leukemia, University of Chicago, Wendy Stock, MD “Dual targeting of suicide blockers and growth promoters for treatment of T-cell Acute Lymphoblastic Leukemia (T-ALL)” T-ALL is an aggressive type of Acute Lymphoblastic Leukemia (ALL) that affects the lymphoid-cell-producing stem cells, particularly a type of white blood cell called T lymphocytes. T-ALL represents approximately 15% of pediatric and 25% of adult of ALL cases.

While survival rates overall have improved during the last decade, 35-40% of patients with T-ALL still relapse, and treatment options are limited beyond first-line therapy. To address this critical need, Dr. Stock is investigating a novel combination therapy in patients with relapsed T-ALL.

Building on preclinical findings published in AACR’s Clinical Cancer Research, Dr. Stock plans to combine LP-118 – an exciting new drug with dual targeting activity to block proteins critical to survival of T-ALL cells – with signaling pathway inhibitors like Dasatinib, or related drugs such as Ponatinib.

This approach represents a strategic combination therapy designed to enhance the effectiveness of leukemia treatment in this patient population that is in urgent need of more options. This grant is in partnership with The Wise Family Foundation and the Leukemia & Lymphoma Society. 2023 Pediatric Cancer, Dana-Farber, Allison F.

O’Neill, MD “2141-V11, An Agonistic Anti-CD40 Antibody, for Pediatric Solid Tumors” Approximately 1 in 285 children in the U.S. will be diagnosed with cancer before their 20th birthday. Most of these cancers originate from solid organs or soft tissues, primarily the brain or extracranial sites.

While advancements in therapies have improved survival rates, treating advanced cases, especially those that have spread, remains challenging and treatment is often associated with long-term toxicities. Immunotherapy, a preferred alternative to standard chemotherapy, has shown promise in adults but the development of immune therapies for pediatric patients has been limited.

To address this critical knowledge gap, Dr. O’Neill is investigating a potential breakthrough treatment involving a new antibody called 2141-V11. This antibody aims to activate immune cells within pediatric solid tumors and enhance the body's natural defenses against cancer.

The antibody targets a receptor called CD40 , found on various immune cells, that when activated can activate the immune cells to better recognize cancer cells directly and stimulate T cell responses— both of which are crucial for fighting cancer.

The primary goal of this study is to evaluate the safety and effectiveness of delivering this antibody directly into the tumor (intratumoral injection) for pediatric patients with solid tumors.

This innovative approach holds promise due to its potential to activate immune cells within the tumor microenvironment, which might overcome the challenges posed by low tumor immunogenicity (ability to provoke an immune response) commonly observed in pediatric cancers.

The results from this study are poised to fill a critical gap in what we know about how the immune system fights cancer in children, and if successful, could pave the way for a new era of targeted therapies that harness the power of the immune system, offering renewed hope for young patients and their families.

2023 Breast Cancer, City of Hope, Aritro Nath, PhD “‘AI and Mechanistic Modeling in Molecular Medicine’ (AIM4) for Treatment of Metastatic ER+ Breast Cancer” Approximately 13% of women born in the US today will develop breast cancer, and of those, ~80% are estrogen receptor-positive.

While there are various FDA-approved treatment options available, oncologists lack an approved biomarker to determine which treatment will be most effective for each individual patient in second-line treatment for these metastatic breast tumors. This advanced study addresses the challenge of determining effective treatments for this type of breast cancer.

Dr. Nath, in collaboration with Dr. Andrea Bild at City of Hope and Dr. Rachel Layman at MD Anderson Cancer Center, has developed an innovative systems biology biomarker approach that analyzes patients' tumor characteristics using genomic data and artificial intelligence.

The trial, known as AIM4 ("AI and Mechanistic Modeling in Molecular Medicine"), involves biopsy samples analyzed through a CLIA-certified biomarker assay, offering personalized treatment recommendations. Their novel "ENDORSE" biomarker, based on patient tumor transcriptome, has shown remarkable predictive performance.

By combining ENDORSE with a new mTOR inhibitor response biomarker, the trial strives to improve progression-free survival outcomes. This groundbreaking trial represents significant progress in tailoring cancer treatment to individual patients.

By understanding the unique characteristics of each patient's tumor, oncologists are equipped with the information they need to select the most effective therapies, ultimately improving patient care and outcomes. The AIM4 trial is a collaborative effort involving City of Hope, MD Anderson Cancer Center, Inova Health System, and Cleveland Clinic.

Dr. Andrea Bild at City of Hope will contribute to the project through intellectual guidance and participation in the strategic decision-making process. 2022 Multiple Myeloma, USC, Kevin M. Kelly, MD "A Phase 1B/2 Study of Bortezomib, Pembrolizumas, and Pelareorep in Patients with Relapsed Multiple Myeloma" Multiple myeloma is the second most common hematologic malignancy.

It is a type of blood cancer that targets plasma cells, causing them to multiply unchecked, taking over space in the bone marrow of those affected, and producing excessive harmful proteins. Multiple myeloma is considered incurable at present. There are many available therapies at initial diagnosis, but most patients experience relapse at one to three years.

Treatment after relapse requires combination therapy to enhance the body’s antitumor immune response. Dr. Kelly and his team have previously combined Pelareorep (Pela) and Bortezomib (Bz) in a trial with a remarkable 55% response rate, significantly more successful than other available rescue therapies.

In the current trial, Dr. Kelly will expand to add Pembrolizumab (Keytruda®), a PD-1 immune checkpoint inhibitor, to allow and enhance the anti-tumor immune response of Pela and Bz. Pela has dramatic PD-L1 immune priming effects (by increasing cell expression of PD-L1) that make it an optimally precise agent to sensitize multiple myeloma cells to immune checkpoint inhibitor therapy.

In the lab, this drug combination demonstrated a significant decrease in disease burden and increased overall survival. This trial will establish the safety and efficacy of this specific combination of medications in patients with recurrent multiple myeloma. It will also evaluate predictive biomarkers of treatment success to aid future trials in this realm.

2022 Ovarian Cancer, Dana-Farber, Rebecca L.

Porter, MD, PhD "A Phase 1b Study of Cytokine-induced Memory Like (CIML) Natural Killer (NK) Cell Therapy in Combination with PD-1 Inhibitor (Spartalizumab) and IL-15 Heterodimer (NIZ985) in Recurrent Ovarian Cancer" This study, led by Dr. Rebecca Porter at Dana-Farber Cancer Institute, examines a novel combination of three synergistic agents: a cellular agent with in vivo durability (pre-activated autologous CIML NK cells), an immunologic agent to enhance biological activity of those NK cells (IL-15 super-agonist), and a novel PD-1 Inhibitor agent to confer greater longevity for therapeutic NK cells (Spartalizumab).

IL-15 super-agonists have already been proven to enhance NK cell cytotoxicity (effectiveness in destroying cancer cells) in vivo studies on ovarian cancer. PD-1 inhibitors have shown efficacy in ex vivo models of ovarian cancer and in current in vivo clinical trials for therapy of other tumor types.

The three agents used in this trial show promising results in other cancer types, but until now, they have remained unexplored in ovarian cancer and the combination is novel.

Dr. Porter says, “While immune-based therapies have been revolutionizing the treatment of some cancers, standard immunotherapies have not been beneficial yet for patients with platinum-resistant ovarian cancer - a disease that has few effective treatment options – and novel combination strategies are critically needed.

” 2021 Bile Duct Cancer, City of Hope, Daneng Li, MD & Mustafa Raoof, MD “Safety and Efficacy of Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) for Treating Peritoneal Metastasis in Cholangiocarcinoma Patients” Cholangiocarcinoma is also called bile duct cancer because its malignancies ravage the body’s passageways — from the liver to the gall bladder — that are essential to digestion.

When cholangiocarcinoma metastasizes to distant sites, the results are lethal for 100% of patients. Current treatments have been unable to extend lives beyond five years after diagnosis, and that five-year survival rate is just 2%. The protective covering of abdominal organs and cavities known as the peritoneum is a common site of recurrence and distant metastases, which occur in 20% of cholangiocarcinoma patients.

The treatment for this metastasis is chemotherapy and the median survival rate is less than a year. Therefore, more effective and less toxic approaches are urgently needed. This grant will fund a Phase I trial testing Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in combination with intravenous chemotherapy.

PIPAC offers an avenue that is minimally invasive and potentially far more effective than current methods of care. PIPAC bypasses the blood-peritoneal barrier that can hamper the effectiveness of intravenous chemotherapy. Pressurization enables the chemotherapy to reach deeper into tissue than previously possible, enhancing effectiveness with only 10-20% of the dose levels required by traditional injection.

This significantly lowers the treatment’s toxicity to healthy tissue. To further reduce side effects, the aerosolized chemotherapy is vacuumed back out after 30 minutes of treatment. This is the first clinical trial of PIPAC in the United States.

2019 Glioblastoma, UCLA, Linda Liau, MD & Tim Cloughesy, MD “Revolutionizing Glioblastoma Treatment: Understanding the anti-tumor immune response to develop novel immunotherapy for glioblastoma” Drs. Liau and Cloughesy co-direct the UCLA Brain Tumor Center, which is one of five brain cancer programs nationwide to be designated a Specialized Program of Research Excellence by the National Cancer Institute.

This trial will focus on adult patients with recurring glioblastoma to develop rational combinations of immunotherapeutic strategies and understand the dynamics of the anti-tumor immune response. The specific treatment includes neoadjuvant immunotherapy with a PD-1 antibody blockade and dendritic cell vaccination.

2018 Bladder Cancer, UCLA, Karim Chamie, MD “Phase II trial testing a hydrogel polymer to target chemotherapy in urothelial cancer. ” TRIAL STATUS: NOT YET RECRUITING In 2013, PHASE ONE funded a Phase I trial led by Dr. Chamie testing a groundbreaking new treatment: a hydrogel polymer to target chemotherapy in urothelial cancer. This treatment is now in an international Phase III trial.

Building on the success of the 2013 trial, Dr. Chamie now plans to use this targeted therapy in patients with metastatic urothelial carcinoma, adding checkpoint inhibitors and immune stimulators to the polymer. A locally delivered treatment would be a paradigm shift, not only in the way checkpoint inhibitors are administered but also in the way physicians can manage the care of metastatic urothelial carcinoma.

“ The role of philanthropy is to support innovative ideas— high-risk, high-reward ideas. And that’s really what PHASE ONE Foundation has done. ” — Dr. Santosh Kesari, Saint John's Cancer Institute 2021 Liquid Biopsy + Early Cancer Detection, City of Hope, Dan J.

Raz, MAS, MD "Defining and Enhancing the Capacity of Liquid Biopsy and Whole-body MRI for Early Cancer Detection in People at Hereditary Risk of Cancer” Individuals with a strong family history of cancer have limited tools available to detect the disease early, when it's most treatable.

To tackle this challenge, PHASE ONE provided funding to Dr. Dan Raz at City of Hope to launch a groundbreaking study evaluating two advanced cancer screening methods: liquid biopsy , a simple blood test detecting early cancer markers, and whole-body MRI , a detailed imaging test identifying cancer before symptoms emerge.

The study enrolled 100 individuals with a strong family history of cancer, demonstrating that these screening tools effectively identified several cancers, including early-stage lung, prostate, duodenal, and ovarian tumors, when treatment success rates are highest. Participants also reported significantly reduced anxiety about developing cancer following screenings.

“This trial is a major first step in our efforts to make screening easier and available to as many people as possible. Early detection is key, and with increased screening, thousands more lives could be saved. PHASE ONE is a critical partner in advancing this groundbreaking work.

” —Dan J. Raz, M. D.

, M. A. S.

The promising results from this study could significantly improve how cancer is detected and prevented. Moving forward, Dr. Raz and his team aim to expand access to these promising screening techniques, evaluate their cost-effectiveness, and ensure equitable availability for diverse patient populations.

2021 Gastrointestinal Tumors (GIST), UCSD, Jason Sicklick, MD “‘Phase II clinical trial for advanced or metastatic gastrointestinal tumors (GIST)” PHASE ONE provided critical funding to Dr. Jason Sicklick to launch a clinical trial evaluating Temozolomide (TMZ) as a treatment option for patients with advanced SDH-deficient gastrointestinal stromal tumors (GIST)— a rare cancer subtype that responds poorly to existing therapies.

The study demonstrated that TMZ effectively stabilized or reduced tumors in over 91% of patients, allowing some previously inoperable cases to undergo successful surgical removal. These results mark significant progress for a patient population with limited options, and Dr. Sicklick's team has now expanded the research to investigate TMZ in combination with other targeted therapies.

The trial also established the first national biobank for SDH-deficient GIST, laying the foundation for future research and treatment breakthroughs.

2020 Acute Myeloid Leukemia, City of Hope, Elizabeth Budde, MD, PhD “Improving Immunotherapy to Target Acute Myeloid Leukemia (AML)” Dr. Elizabeth Budde’s ongoing study for Phase I Acute Myeloid Leukemia studies new therapies to target CD123, a protein associated with AML— one of the deadliest forms of leukemia. The Phase I trial found favorable results in patients treated with CD123-CART cell therapy.

However, the protein CD33 is found to be in 95% of the samples of patients with AML and increases with treatment using the drug decitabine. Dr. Budde’s team is one of the first to create a CART cell therapy to treat patients with AML. Using T cells from leukemia patients and a leukemia mouse model, her team formed a CD33 antibody to target CD33 leukemic cells.

With the addition of the antibody CD33-CART, cells kept their killing efficacy but did not exhaust. Dr. Budde is confident that CD33-CART therapy is ready to be submitted for FDA approval, hoping to start a clinical trial in 2022.

2020 Prostate Cancer, UCLA, Wayne Brisbane, MD & Leonard Marks, MD “Micro-Ultrasound for Detection and Localization of Prostate Cancer Prostate cancer is a common and serious disease, with 175,000 new cases and 32,000 deaths expected this year. MRI imaging has improved early diagnosis of prostate cancer, but MRI is cumbersome and expensive.

A micro-ultrasound system, which provides high-resolution images not previously available, has the potential to replace MRI and can be used in a doctor’s office. Drs. Brisbane and Marks evaluated this new system and compared micro-ultrasound and magnetic resonance imaging (MRI) to final pathology in men undergoing prostate removal.

The study enrolled more than 40 patients toward a study endpoint of 90 patients; making novel engineering advances in image registration; and generating preliminary data for future National Institutes of Health (NIH) funding. The interim analysis demonstrated that micro-ultrasound had high sensitivity for locating tumors and delineating tumor margins.

All index lesions (the drivers of metastasis and death) were visualized with micro-ultrasound— a level of accuracy in imaging registration that had never previously been attained for this system. Thanks to support from PHASE ONE, early data generated from this project will demonstrate the feasibility of this study design for the NIH.

The novel imaging investigations and research methods PHASE ONE made possible will benefit patients and researchers.

2020 Osteosarcoma, Children's Hospital Los Angeles, Fariba Navid, MD & Leo Mascarenhas, MD, MS “A Phase ll Study of Regorafenib in Combination with lmmune Checkpoint lnhibitor Nivolumab in Patients with Refractory of Recurrent Osteosarcoma” Osteosarcoma is the most common malignant bone tumor in children, adolescents, and young adults.

This grant will fund a Phase II study that brings a brand new approach to the treatment of patients with refractory or recurrent osteosarcoma, combining the drug regorafenib with an immunotherapy called nivolumab.

This trial aims to make a broad-scale impact across the age spectrum, and it has the potential to open a new path forward for this life-threatening disease that has not seen any successful attempts at alternative forms of therapy in the past 30 years.

2018 Rhabdomyosarcoma, UCLA, Noah Federman, MD & Arun Singh, MD “A Phase I/II Study Of Novel HDAC inhibitor Mocetinostat in combination with vinorelbine in relapsed/refractory Rhabdomyosarcoma” Rhabdomyosarcoma, a tumor that starts in skeletal muscle, is a rare and devastating disease mostly found in children.

New approaches are needed for patients who relapse on standard treatments as there have not been any new treatment developments in this area in 30 years and only chemotherapies are currently available. Moreover, the lack of good model systems, limited funding for this rare disease, and a lack of interest from pharmaceutical companies have hindered drug development in this area.

Through high throughput profiling of cancer cells in the Translational Oncology Research Labs at UCLA, a new candidate drug has been identified that may have efficacy in this patient population. We have done additional research to validate this finding and have isolated a combination treatment approach with this new molecule that would be a valid clinical strategy in the refractory rhabdomyosarcoma population.

We have garnered approval to use this medicine and have put together a clinical trial for the use of this medicine. Teaming up with Phase One has been instrumental in providing much-needed funding to execute this clinical trial and bring a novel drug combination to rhabdomyosarcoma patients with few choices. 2018 Head and Neck Cancer, UCLA, Maie St.

John, MD “Precision cancer surgery using Dynamic Optical Contract Imaging” Dr. St. John worked with a team from the engineering department at UCLA and created a tool that uses non-invasive imaging to detect between normal and cancerous tissue.

This intraoperative instrument is the first of its kind and will reduce the devastating side effects of surgical resection of a tumor and improve the precision of cancerous tissue that is removed, leading to a potential impact on cancer mortality.

2018 Liver Cancer, UCLA, Noah Federman, MD “Precision pediatric liver cancer therapy using high-throughput drug screening of patient-derived tumor organoids” Liver cancer is rare in children, adolescents, and young adults, but when aggressive malignancies are found, the patients often require intense chemotherapy, aggressive surgery, and a potential liver transplant.

This trial will use a unique approach to personalized medicine, by screening primary-culture-3D tumor organoids from surgically removed pediatric liver cancer specimens. This method will allow hundreds to thousands of drugs to