MEDICAL GRANTS

“APG-157 and Immune Checkpoint Inhibitors for Treatment of Head and Neck Cancer"

$80,000 Medical Grant

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.

“Sensitizing Pancreatic Cancer to Immunotherapy”

$370,240 Medical Grant

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.

“Phase I Trial of Tazemetostat in Combination With Venetoclax in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma”

$360,864 Medical Grant

TRIAL STATUS: RECRUITING

Non-Hodgkin lymphomas contribute to 77,000 new cancer diagnoses annually in the US. The current standard treatment is chemotherapy, which exhibits limited effectiveness and notable toxicity. The need for targeted, chemotherapy-free approaches is clear.

Recent advancements in genetic sequencing have provided insights into the unique vulnerabilities of non-Hodgkin lymphomas. Dr. Roth's research identified specific genetic subtypes responsive to a combination of two non-chemotherapy drugs: venetoclax, targeting a cell death regulatory protein, and tazemetostat, focusing on the epigenome. Both medications have been studied in patients with leukemia and lymphoma and have been shown to be safe, however, they have not previously been used in combination.

This combined approach has the potential to revolutionize treatment by precisely targeting the molecular pathways crucial to cancer cell development, progression, and survival—which could potentially enhance efficacy compared to using either medication alone.

The primary objective of the trial is to assess the safety and tolerability of the combination treatment for patients with non-Hodgkin lymphomas (specifically patients with either diffuse large B-cell lymphoma or follicular lymphoma) whose disease has returned after having received prior treatment (relapsed), or whose disease has failed to respond to prior treatments (refractory).

To achieve this, Dr. Roth will conduct a two-part clinical trial where patients will ingest oral medication and attend regular clinic visits for blood tests and imaging to oversee potential side effects and track the progression of cancer.

Part 1 involves a dose escalation of venetoclax to identify the optimal dose to be given with tazemetostat– maximizing the therapeutic benefits while minimizing severe side effects. Part 2 will focus on expansion cohorts to further characterize the safety and tolerability of the combination and evaluate early signs of efficacy.

PHASE ONE’s grant provides funding for Part 2 of the trial, and expansion to three additional sites, which will help increase patient accrual.

This study has the potential to advance treatment for non-Hodgkin lymphomas while avoiding toxic chemotherapy for patients in need of new and better therapeutic options.

“Dual targeting of suicide blockers and growth promoters for treatment of T-cell Acute Lymphoblastic Leukemia (T-ALL)”

$250,000 Medical Grant

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.

“2141-V11, An Agonistic Anti-CD40 Antibody, for Pediatric Solid Tumors”

$370,000 Medical Grant

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.

“‘AI and Mechanistic Modeling in Molecular Medicine’ (AIM4) for Treatment of Metastatic ER+ Breast Cancer”

$397,000 Medical Grant

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.

"A Phase 1B/2 Study of Bortezomib, Pembrolizumas, and Pelareorep in Patients with Relapsed Multiple Myeloma"

$150,000 Medical Grant

TRIAL STATUS: RECRUITING

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.

"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"

Grant Amount: $287,602

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.”

"Defining and Enhancing the Capacity of Liquid Biopsy and Whole-body MRI for Early Cancer Detection in People at Hereditary Risk of Cancer”

Grant Amount: $300,000

TRIAL STATUS: RECRUITING

People with a strong family history of cancer currently have limited options for early detection of the disease. The noninvasive techniques of liquid biopsy — which tests blood samples for signs of circulating tumor cells or tumor DNA — and whole-body magnetic resonance imaging (WB-MRI) are among the most promising technologies for detecting cancer before any symptoms appear. Several liquid biopsy platforms are in development and close to clinical availability, and while WB-MRI is currently recommended for certain rare hereditary cancer syndromes, but has not been widely adopted as a general screening option. This study aims to help make these assessments more available to those with strong family histories of cancer. This study will be patient-centered with attention given to the effects of these studies on fear of cancer, psychological distress, and health economics (to measure downstream costs), as well as equity and inclusion to ensure that diverse populations have access to comprehensive screening.

“Safety and Efficacy of Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) for Treating Peritoneal Metastasis in Cholangiocarcinoma Patients”

$300,000 Medical Grant

TRIAL STATUS: RECRUITING

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.

“‘Phase II clinical trial for advanced or metastatic gastrointestinal tumors (GIST)”

$500,000 Medical Grant

Although there are treatment options for advanced or metastatic gastrointestinal tumors (GIST), these therapies are known to be largely ineffective in a much rarer subtype that is deficient in succinate dehydrogenase (SDH), a protein that is important for making energy for the body.

The grant will support a Phase II clinical study to investigate how patients with mutant SDH (mSDH) GIST respond to treatment with Temozolomide, a therapy approved for patients with newly diagnosed glioblastoma multiforme and refractory anaplastic astrocytoma cancers.

“Revolutionizing Glioblastoma Treatment: Understanding the anti-tumor immune response to develop novel immunotherapy for glioblastoma”

$400,000 Medical Grant

TRIAL STATUS: RECRUITING

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.

“Phase II trial testing a hydrogel polymer to target chemotherapy in urothelial cancer.”

$277,000 Medical Grant

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.

“A Phase I/II Study Of Novel HDAC inhibitor Mocetinostat in combination with vinorelbine in relapsed/refractory Rhabdomyosarcoma”

$100,000 Medical Grant

TRIAL STATUS: RECRUITING

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.

“Improving Immunotherapy to Target Acute Myeloid Leukemia (AML)”

$100,000 Medical Grant

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.

“Micro-Ultrasound for Detection and Localization of Prostate Cancer

$100,000 Medical Grant

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.

“A Phase ll Study of Regorafenib in Combination with lmmune Checkpoint lnhibitor Nivolumab in Patients with Refractory of Recurrent Osteosarcoma”

$350,000 Medical Grant

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.

“Precision cancer surgery using Dynamic Optical Contract Imaging”

$297,000 Medical Grant

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.

“Precision pediatric liver cancer therapy using high-throughput drug screening of patient-derived tumor organoids”

$100,000 Medical Grant

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 be tested directly on cancer tissues harvested from patients. These results will lead to proven and individualized treatment based on specific tumor and personal characteristics.

“Using personalized medicine to change the standard of care: Clinical trial of precision immunotherapy in the neoadjuvant setting for patients with glioblastoma

$299,000 Medical Grant

Patients with high-grade gliomas represent a population with a large unmet medical need, and many drugs have failed to be effective enough to change the standard of care over the past 20 years. Standard therapy includes surgery followed by radiation and chemotherapy. However, radiation can cause immunosuppression, cognitive decline, and other unwanted side effects, as well as promote more aggressive tumor recurrence.

Traditionally, new drugs in development are not tested in clinical trials until after the tumor has recurred at least once. At this point, the tumor is highly resistant to all therapies, and the patient’s immune system is compromised.

New strategies are needed to understand how drugs affect individual tumors and the immune system to kill cancer. Therefore, early testing of new therapies is likely to be more effective when the immune system is still intact.

In this study, Dr. Kesari plans to use the immune system to kill cancer (immunotherapy) based on individual tumor and patient characteristics (precision), before standard radiation therapy (neoadjuvant).

“Immunotherapy with Natural Killer Cells for Treatment of Neuroblastoma”

$61,000 Medical Grant

Neuroblastoma is the most common extra-cranial solid tumor in children. Patients with high-risk features continue to have an expected survival of 50% despite intensive therapy. The addition of immunotherapy utilizing the recently FDA-approved anti-GD2 mAb ch14.18 Unituxin has improved outcomes. However, long-term disease-free survival remains a significant problem, and improving immunotherapy further is needed for complete disease eradication of the disease.

Adoptive immunotherapy with natural killer (NK) cells has emerged as a promising anti-cancer treatment with broad anti-cancer potential. Until recently, the clinical efficacy and effective application of NK cell immunotherapy have been limited by the inability to obtain sufficient cell numbers for adoptive transfer. Dr. Marachelian has developed a novel expansion method for NK cells that solves this problem using artificial antigen-presenting cells to express stimulatory molecules that promote sustained proliferation of NK cells in the laboratory. This expansion can be performed from blood from a simple venipuncture that can then be sent to the central laboratory.

This Phase I study will be the first study to combine cellular therapy with Unituxin in the treatment of patients during which we will identify the maximum tolerated dose of NK cells to be given with Unituxin and determine the immune effects of the combination therapy for patients with neuroblastoma. It will also be the first multi-center pediatric trial with cellular therapy and will help pave the way for other cellular therapy trials in pediatrics. The trial will be conducted through the NANT consortium (NANT.org), a multi-institution consortium (centered at CHLA) whose goal is to identify new therapies for patients with relapsed and refractory neuroblastoma and to improve their outcome. If successful, this therapy could then be utilized for all high-risk neuroblastoma patients to eradicate residual disease.

“Undergraduate degree program at the USC Jimmy Iovine and Andre Young Academy for Arts, Technology and the Business Innovation in partnership with the Convergence Science Initiative in Cancer”

$425,000 Medical Grant

In 2017 The USC Lovine and Young Academy for Arts, Technology, and Business Innovation partnered with Dr. Peter Kuhn and Convergence Science Initiative in Cancer. With help from PHASE ONE, the Academy launched a four-year track that applies its educational model to the health field to help boost innovation in patient care. The track includes undergraduate students working hands-on with physicians, cancer patients, scientists, and graduate students while immersed in research and information-filled environments. The program aims for students to help develop and create solutions that advance patient outcomes changing the future of cancer research and treatments.

“Phase I Study of CD-Expressing Neural Stem Cells in Combination with Oral 5-FC in Patients with Recurrent High Grade Gliomas

$66,000 Medical Grant

Treating brain tumors with chemotherapy presents special challenges because the blood-brain barrier restricts which chemicals can reach the vast majority of our brain cells. The barrier consists of a network of junctions between our capillaries and the brain cells that they supply with blood. These junctions possess an electrical resistance that permits water, certain gases, lipids, glucose, and some amino acids to pass through, but other substances are blocked – creating a significant hurdle to delivering medication.

PHASE ONE immediately saw the potential benefits of Dr. Portnow’s proposal to use neural stem cells to circumvent the blood-brain barrier and deliver targeted chemotherapy to tumor sites.

The trial began in 2010 with the first-in-human study and concluded in January 2013 with 15 enrolled patients. In addition to the groundbreaking work being conducted within the brain, Dr. Portnow’s team also tested whether they could use a microcatheter to provide a continuous supply of stem cells to the brain in order to eliminate the need for a surgical infusion each time. Indeed, their work with the microcatheters was able to document proof-of-concept.

Work continues in this promising field, with the intent that another trial group will soon be able to undergo treatment with microcatheter delivery of stem cells.

In 2014, brain cancer was the focus of PHASE ONE’s award-winning video – EveryONE Can Make a Difference. After its premiere, guests at the Gala were able to donate directly to Dr. Portnow’s work— raising an additional $67,000.

Funding is limited for this area of study, so PHASE ONE's support has been pivotal in advancing its progress in recent years. Without these resources – and the additional funds that have been leveraged with them, stem cell treatment of brain tumors might not have emerged as the promising therapy that it is.

“A Phase I Study Of Veliparib (ABT-­‐888) in Combination with Gemcitabine and IMRT in Patients with Locally Advanced Pancreatic Cancer”

$323,000 Medical Grant

In 2014, Dr. Richard Tuli conducted a Phase I study to examine the safety and competence of a new combination therapy for advanced pancreatic cancer— a devastating disease with the lowest survival rate of any solid cancer.

This trial successfully found the safest and most effective dose of veliparib in combination with gemcitabine and radiotherapy. As a result, levels of inflammatory markers increased significantly, creating a molecular signature with potential to serve as a biomarker to predict how the patient and tumor will respond to treatment.

This study was a crucial step forward in the ability to personalize treatments using PARP1/2 inhibitors.

“The utility of a novel hydrogel polymer in the diagnosis and treatment of urothelial carcinoma”

$142,000 Medical Grant

Dr. Karim Chamie, with UCLA urologists, pinpointed a solution for the ongoing clinical dilemma surrounding Urothelial Carcinoma, the fourth most common cancer in men and fifth overall.

Using a hydrogel polymer, a liquid at room temperature, and mixing it with chemotherapeutic agents, it distributes high doses of chemotherapy to the tumor, reducing absorption and side effects. Before the establishment of Polymer-chemotherapy, many other methods failed because of the lack of visualization of cancer in the kidney using scopes and also maintaining the chemotherapy exposure time due to how fast the kidney and ureter drain into the bladder.

The trial was a success as Dr. Chamie and his team used Polymer-chemotherapy to deliver high doses of chemotherapy with minimal drainage and side effects.

“Purchase of a Hamamatsu NanoZoomer 2.0-HT Slide Scanner”

$75,000 Medical Grant

PHASE ONE board member and former chair, Tia Palermo, passed away in 2012 following an 11-year battle with cancer. PHASE ONE wanted to honor her memory, and along with generous donations from friends and family, funded an extraordinary piece of equipment called the Hamamatsu NanoZoomer 2.0 HT-slide scanner at City of Hope, where Tia had been treated.

The T Cell Therapeutic Research Laboratory (TCTRL), directed by Tia’s physician Dr. Stephen Forman, is developing novel immune-based therapies for the treatment of cancer—specifically for the treatment of hematological malignancies, gynecological cancers and brain tumors. Their pre-clinical and clinical research program focuses on engineering human T cells to recognize and destroy tumor cells, and, in first-in-human clinical trials, in which a patient’s own reprogrammed tumor-specific T cells are transferred back to that patient, have observed encouraging initial results. A current technical challenge for the research program is the high-throughput evaluation of human and mouse tumor and organ histology both before and after therapeutic intervention with T cells that have been genetically modified to attack tumors. To address this technical limitation, the goal was to purchase the Hamamatsu NanoZoomer 2.0-HT slide scanner (C9600-13)with fluorescence imaging module (L11600-21). This equipment has helped evaluate the amount of T cell and/or tumor cell engraftment in their in vivo models of cancer therapy, and the surface marker/antigen profiles of individual cells both in their in vivo cancer models as well as on primary human tumor samples. Specifically, this slide scanner and imager provide cell-level resolution critical for determining the frequencies of varying patterns of antigen expression, mapping antigen distributions between cells and on individual cells both before and after adoptive T cell therapy in clinical trials and/or animal experiments.

The Hamamatsu unit combines high capacity (210 slides per run) for array tomography mapping of antigen expression relative to tumor structures, high resolution (0.46μm/pixel or 0.23 μm/pixel), and high sensitivity with relatively increased speed with TDI (Time Delay Integration) line scanning. Cell-level resolution is critical for determining frequencies of varying patterns of antigen expression, mapping antigen distributions between cells and on individual cells. The COH Light Microscope and Digital Imaging Core, while well-equipped for conventional confocal microscopy, lacks the capability for scanning wide fields at high spatial resolution and high throughput. Overall, this slidescanner and imaging unit is extremely important for their research mission of developing cancer immunotherapies.

“Pilot Study to Assess More Effective Therapies for Patients with Advanced Ewing's Sarcoma”

$37,000 Medical Grant

City of Hope launched a five-year pilot clinical trial to study the effectiveness of a promising treatment for high-risk patients with advanced Ewing’s sarcoma— one of the most common bone tumors in adolescents. The new treatment will consist of whole-body MRI-guided radiation therapy followed by autologous hematopoietic cell transplant, with a novel combination of high-dose chemotherapy. The study will assess whether this therapy is feasible, safe and likely to increase patient survival rates.

PHASE ONE provided seed funding to help young patients with Ewing’s sarcoma access a promising new therapy by supporting MRI tests for patients not covered by their insurance.

“Clinical Validation of MicroRNA/RNA Predictive Biomarkers and Therapeutic Targets Overcome Mechanisms of Immunotherapy Escape in Patients with Metastatic Kidney Cancer”

$310,000 Medical Grant

UCLA Urology’s Allan Pantuck, MD, and Arie Belldegrun, MD, along with Joseph Riss, PhD, have been working for years to develop innovative methods of therapy for treating metastatic kidney cancer. In 2013, Joseph Riss initiated an innovative and multidisciplinary three-year translational research project to develop serum- and urine-based gene expression and microRNA predictive biomarkers and then utilize these markers to develop rational combination therapies to overcome treatment resistance. This study provided an initial proof-of-concept for the specificity, efficacy, safety, and activity of the DC-Ad-GM∙CAIX mono-immunotherapy, forming the basis for a first-in-human phase I trial in ccRCC patients.

This research had a transformative impact on tumor immunology, creating a new foundation of genetic and molecular biomarkers.

“A Phase I Study of Gene Modified Immune Cells and a CTLA4 Antibody in Patients with Advanced Melanoma”

$252,000 Medical Grant

With the support of the PHASE ONE Foundation Dr. Antoni Ribas and his team will conduct a Phase I clinical trial (MART-1 F5 TCR Engineered Adoptive Cell Transfer Therapy with CTLA4 Blockade) with the goal of genetically programming the human immune system to efficiently target cancer cells in patients with advanced stage melanoma, the deadliest of skin cancers. This clinical trial builds upon the experience at UCLA over the past 3 years in the use of T cell receptor (TCR) engineered adoptive cell transfer therapy. This therapy is manufactured in-house and results in the generation of a large army of immune system cells that are genetically redirected to recognize and kill melanoma. With this therapy, we have noted high initial response rates, but tumors come back. A major limitation has been a progressive decrease in the antitumor functionality of the TCR-engineered immune cells. The antibody tremelimumab blocks a major negative regulator in immune cells and will be tested with the goal of maintaining the cancer-killing functionality of the TCR-engineered lymphocytes given to patients. This protocol has administrative approval by the UCLA regulatory committees and it has already been filed and approved by the Food and Drug Administration.

“Combined Cytotoxic and Immune-Stimulatory Therapy for Glioma”

$216,000 Medical Grant

Dr. Pedro Lowenstein and Maria Castro created a new form of therapy combining gene therapy and immunotherapy as a new approach to treating brain tumors, one of the most untreatable and fatal cancers.

Their process uses one adenoviral vector expressing protein Flt3L for dendritic cells in the brain, while the second adenoviral vector represents the protein HSV1-TK, later activated by valacyclovir, killing tumor cells.

This process triggered a systemic immune response, allowing the assembly of anti-glioma cytotoxic T-cells. The FDA gave the green light for Dr. Lowenstein and his team to begin their human trial funded by PHASE ONE.

Promising initial outcomes were observed with these therapies, demonstrating enhanced survival rates. Out of the 18 participants in the trial, six lived beyond two years, three surpassed three years, and one patient, still alive at the time of publication, endured for up to five years.

In contrast, the standard of care presently offers a life expectancy of just over 14 months for this type of tumor.

Additionally, the treatment exhibited non-toxicity in patients, indicating that the highest dosage administered in this trial might be feasible for future studies.

“Finally, after many years, we’re thrilled to report the results of testing this approach in human patients, obtaining results that will lead to better treatments for this group of brain tumor patients,” - Maria Castro, PhD

Despite the anticipated one-month activity of the adenoviral gene therapy vectors, this trial revealed that the adenoviral vector expressing HSV1-TK remained active for an extended period, up to 17 months.

This finding alters expectations for adenoviral gene therapy in the brain and prolongs the potential timeframe for utilizing the combination of HSV1-TK and Valtrex to combat tumor recurrence.

While further research is essential before clinical implementation, the noteworthy extended expression of HSV1-TK implies its potential for enhancing treatment.

The outcomes of this study provide support for the formulation of future Phase 1b/II clinical trials.

To learn more about Drs. Castro and Lowenstein’s pioneering trial – click here to watch their TEDx talk.

“A Phase I Study of AC220 for Children with Relapsed or Refractory ALL or AML”

$410,000 Medical Grant

In 2010, Dr. Stuart Sigel pursued his study on improving the clinical outcomes of childhood leukemia. Dr. Sigel first pursued the study of the drug AC220 in Phase I childhood leukemia, and he continued his study funded by PHASE ONE to identify the approved dose of AC220 for Phase II. His study successfully found the recommended and safe dose of AC220 for treatment. Dr. Sigel and his team were able to reach their goals of the study as all patients who completed the trial were able to be evaluated for toxicity and response. An abstract of the trial was submitted to the American Society of Hematology and presented in a meeting, and all data collected was analyzed and publicized.

“Establishing a Research-Focused Phase I Lung Cancer Initiative”

$266,000 Medical Grant

Premiere Oncology Foundation, a non-profit dedicated to cancer research, integrative medicine, patient/family support services, and community education, utilized the grant to support a comprehensive lung cancer program to include multi-disciplinary research.

Lung cancer is the world’s top cancer killer, claiming more than 1.3 million lives per year, yet few financial resources have been dedicated to this disease. The Premiere Oncology Foundation Lung Cancer Initiative focuses on the use of FDA-sanctioned novel treatment regimens in collaboration with experts in the field of lung cancer detection and treatment. The program fostered dialog among practitioners caring for lung cancer patients and provided a means for seamless interaction with medical and radiation oncologists, thoracic surgeons, radiologists, pulmonologists, and primary care physicians caring for these patients.

Dedicated to whole-patient care and recognized for expediting clinical trials, Premiere’s flagship cancer center in Santa Monica offers patients the newest cutting-edge treatments, rapid access to novel, internationally available therapies, and integrative medicine all under one roof. Additionally, Premiere provides services in its Scottsdale, Arizona center and research affiliation with Pacific Hematology & Oncology Associates in San Diego.

“Phase I study of UDCA with 5-fluorouracil, leucovorin, oxaliplatin and bevacizumab for metastatic colorectal cancer”

$46,000 Medical Grant

In 2007, Dr. Lily Lai was awarded a grant of $46,839 to start a Phase I trial evaluating the safety of a bile acid called ursodeoxycholic acid (UDCA) in combination with standard chemotherapy and monoclonal antibodies for colorectal cancer that has spread to other areas (metastasized). Dr. Lai hypothesizes that UDCA affects a nuclear receptor called FXR, which has been shown in other studies to suppress intestinal tumors. Targeting receptors such as FXR would enable physicians to offer more personalized treatment to patients with advanced colorectal cancer.

With PHASE ONE’s funding, Dr. Lai determined that UDCA was safe and well-tolerated by patients in combination with chemotherapy. In addition, her initial results indicate that UDCA may alter serum glucose control, although further research is needed to confirm these results and decipher the process by which UDCA and FXR limit tumor growth.

$345,000 Medical Grant

The City of Hope Division of Medical Oncology and its Department of Clinical and Molecular Pharmacology, directed by Yun Yen MD, PhD, is the City of Hope Comprehensive Cancer Center equivalent to a Phase I Solid Tumor Program. This program is the exciting translation of molecules from the laboratory to the clinic.

City of Hope used the PHASE ONE funding to support novel Phase I clinical trials developed in collaboration with the Department of Clinical and Molecular Pharmacology. City of Hope established competitive awards ($25–50K/year for two years) that combined a laboratory and clinical Principal Investigator and translated laboratory observations into the clinic during this period. Programs in Solid Tumors and Hematologic Malignancies including lymphomas, in both adults and children were included.

$2,000,000 Medical Grant

With visionary philanthropy from the PHASE ONE Foundation, Dan Theodorescu, MD, PhD, continues to lead researchers at Cedars‑Sinai in advancing discovery and clinical care. PHASE ONE's investment nurtures research that will result in novel, next-generation treatments that may improve patient outcomes here at Cedars‑Sinai and beyond.

Thanks to PHASE ONE's support, Dr. Theodorescu had time to focus on his role as director of Cedars‑Sinai Cancer, including fostering the opening of Phase I clinical trials. He also had a chance to support Cedars-Sinai's clinical research investigators to initiate the development of trials that address the cancer burden and disparity in the community we serve. Cedars‑Sinai Cancer currently has over 43 active Phase I clinical trials open for enrollment.

When Dr. Theodorescu arrived at Cedars‑Sinai, the cancer program was ranked 41st in the country; this year, US News & World Report (20212022) ranked our cancer program as #9. These exceptional achievements owe a significant debt of gratitude to PHASE ONE's dedicated generosity.

“Phase I clinical trial of mFOLFOX6 and everolimus in patients with metastatic gastric cancers”

$50,000 Medical Grant

PHASE ONE’s support provided Dr. Vincent Chung with critical funding to launch a new clinical trial for patients with advanced gastric cancers. The study not only offered patients access to a promising experimental therapy, it also offered an opportunity to study the gene mutations occurring in gastric tumors and identify biomarkers to help predict response to treatment. The results showed minimal side effects that were treatable with antibiotics, patients did well with a lower dose of chemotherapy/treatment, and the tumors responded positively to treatment.

The trial was completed in 2017, and Dr. Chung continues to pursue this promising line of research. If he can effectively determine which patients will respond to treatment prior to starting chemotherapy, thousands of patients could avoid unnecessary treatment and the toxicities of an ineffective therapy.

“A Phase I Pharmacokinetic and Pharmacodynamic Study of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) in Patients with Localized Prostate Cancer”

$250,000 Medical Grant

Dr. Kuk-Wha Lee launched a Phase I study to determine a biologically effective dose of IGFBP-3 that will induce programmed cell death in men with localized prostate cancer. IGFBP-3 is an important regulator of cancer cell growth and survival and Dr. Lee’s work was instrumental in advancing the field, including important early studies in humans like the one funded by PHASE ONE. While the proposed drug never made it to the market, the investigators believe the greatest impact could be that the class may be useful in cancer, albeit with a need to develop a different preparation.

“A Phase I Trial of Vaccine Therapy Administered Directly into the Tumor in Patients with Lung Cancer”

$150,000 Medical Grant

Cancer treatment breakthroughs typically occur with the discoveries of new drugs or radiology techniques but, thanks to the groundbreaking work of Dr. Karen Reckamp, we have witnessed the development of an innovative lung cancer treatment based on the well-known arthritis medication Celebrex.

Celebrex was introduced in 1998 as an anti-inflammatory. While at the University of California, Los Angeles, Dr. Reckamp approached PHASE ONE with a novel proposal for treating lung cancer with Celebrex to boost the body’s own immune response to cancerous tissues. After completion of the pre-clinical work at UCLA, Dr. Reckamp moved the trial to the City of Hope where she oversaw the phase one study with seven enrolled patients.

Dr. Reckamp’s research and trial determined that Celebrex’s anti-inflammatory effects could reveal the cancer cells to our immune systems. Once they were unmasked, the body’s natural immune response was triggered and the cancer cells were attacked, leading to a reduction in cancer tissue.

Just 10 years ago there was little interest and a scarcity of funding for this area of research. Because of results like we are seeing from this research – which is the direct result of PHASE ONE’s support, there are now other immune-modulating drugs in development that may prove even more effective in treating lung cancer.

“Optimal Deployment of Kinase Inhibitors for Glioma Therapy”

$250,000 Medical Grant

In 2004, the UCLA Jonsson Comprehensive Cancer Center UCLA Jonsson Comprehensive Cancer Center Hematology/Oncology Translational Scientists began working on molecular mechanisms that underlie the development and spread of cancer.

The basic research in this study led to the development of the drug enzalutamide (Xtandi®), which was FDA-approved in 2012.

“A Randomized Phase II Study of Bevacizumab in Combination with Cetuximad plus Irinotecan, or in Combination with Cetuximab Alone, in Irinotecan-Refractory Colorectal Cancer”

$250,000 Medical Grant

Dr. Heinz-Josef Lenz and Dr. Daniel Vallovehmer investigated a novel combination therapy to improve outcomes for patients with irinotecan-refractory colorectal cancer. Their approach was to target both the cell growth and survival signaling pathways to induce improved antitumor activity. Based on the data generated from this trial, Drs. Lenz and Vallovehmer led the way in molecular characterization— resulting in a large number of publications, NIH grants, and changing the paradigm of colon cancer.

After PHASE ONE's funding, Dr. Lenz became the Chair for Correlative Science of the Intergroup 80405 Trial, the largest colon cancer trial ever conducted with over 40,000 biospecimens collected.

The impact of this study was tremendous and transformed how patient treatments and the molecular characterization of colon cancer.

“A Phase I/II Kidney Cancer Vaccine Trial Using Autologous Dendritic Cells Genetically Modified to Express a GMCSF-CAIX Fusion Gene”

$250,000 Medical Grant

In 2004 Dr. Aerie Belldegrun and Dr. Alan Pantuck began a Phase I trial to test the efficiency and safety of an Ad-GMCSF-CAMIX vaccination for patients suffering from Renal Cell Carcinoma. The antibody ABX-EGF locates tumor cells to kill them or release tumor-killing substances to the tumor while also keeping the normal cells unharmed. The goal was to gain enough data and information to develop immune-based therapies to help all kinds of solid tumors.

Thanks to the funding from PHASE ONE and their impressive work, Dr. Belldegrun and Dr. Pantuck were awarded the NCI-Rapid Access to Intervention Development (RAID) grant, which assisted in constructing the vaccine and expanding research— which resulted in a drug that sold for over 11 billion dollars to Kite Pharma.

“Serum Protein Profiling to Predict Outcome of HER-kinase Targeted Therapy”

$250,000 Medical Grant

Dr. David Agus and Dr. Mitchell Gross worked with Cedars-Sinai Prostate Cancer Program to grow the technology to quicken clinical trials by assessing which drug is best for particular patients with prostate cancer. Their team aimed to obtain serum protein profiles for patients treated with HER, followed by a machine to define the serum profile to predict therapy responses.

Using the funds from PHASE ONE, they opened two Phase I trials where they gathered hundreds of serum and plasma samples from patients and sponsors. Additionally, they expanded instrumentation by purchasing two mass spectrometers to aid the sample processing. From the data collected, Drs. Agus and Gross were encouraged to apply for additional funding from outside sources, including the National Cancer Institute, to become a Center of Cancer Nanotechnology Excellence.

With their extensive research supported by PHASE ONE, this study led to a breast cancer drug that is currently on the market!

“Companion to Phase I Study of a Loading Dose Followed by Daily Administration of SU11248 in Patients with Advanced Solid Tumors: CT/PET as Surrogate Marker of Angiogenesis”

$276,000 Medical Grant

In 2003, Dr. Lee Rosen conducted a Phase I study of a medication that could theoretically shut down the development of new blood vessels from which tumors grow and possibly spread. Using a series of radiographic assessments including CT/MRI/Bone scans, etc. as well as conventional scans such as CT/MRI, Dr. Rosen and his colleagues at the Cancer Institute Medical Group, examined the response of their patients to this new medication and to what degree. He also found the use of PET scans, which look at changes in tumor metabolic activity rather than size, is very effective, PHASE ONE has been sponsoring a trial which will look at whether a combination of PET/CT scans can aid in the assessment of the drug’s efficacy more quickly than conventional CT scanning alone.

“Proteasome-inhibitor PS-341 in the treatment of refractory Diffuse Large B-Cell Lymphomas (DLBCL): Clinical efficacy, mechanisms of resistance, and new models of combination-therapy”

Grant Amount: $150,000

Therapy-resistant diffuse large B-cell lymphomas (DLBCL) pose an unresolved clinical problem and most patients die of their disease within months. Several decades of clinical research using different combinations of chemotherapy have not improved survival. Clearly, new therapeutic approaches are needed.

For that purpose, PHASE ONE sponsored an Interdisciplinary Grant to study the use of the Proteasome Inhibitor PS-341 in the treatment of refractory diffuse large B-cell lymphomas in terms of clinical efficacy, mechanisms of resistance, and new models of combination therapy. The study was conducted by principal investigator, Sven de Vos, MD, and co-investigators, Christos Emmanouilides, MD, William H. McBride, MD, and Jonathan W. Said, MD at the Jonsson Comprehensive Cancer Center. The collaboration was very productive.

"We would not have been able to perform and continue these studies without the PHASE ONE grant support. This grant has allowed me to establish my research laboratory here at UCLA and to successfully compete for additional - research funding. Based on the work in this interdisciplinary grant, a novel project has been formulated, aiming at the EBV-virus as a specific anti-lymphoma target. I have submitted a grant proposal regarding this project to the NIH. This project is also part of a Specialized Center of Research (SCOR) grant proposal to the Leukemia and Lymphoma Society headed by Drs. Owen Witte and Charles Sawyers." — Dr. Sven de Vos

“Sponsored Recruitment of Clinical Research Physician”

Grant Amount: $175,000

PHASE ONE sponsored the recruitment of a full-time clinical research physician for a full year. Highly respected oncologist, Dr. Carolyn Britten, joined the faculty of the Jonsson Comprehensive Cancer Center in early 2001 and PHASE ONE funded her research for one year. Dr. Britten is involved in four promising Phase I trials testing new and unique therapeutic strategies in signal transduction and angiogenesis.