About
PHASE ONE

Letter from the
Board Chair

Medical
Grants

Community
Grants

Clinical Trials
Q&A

Thank
You

Looking back on 2024, one word stands out: gratitude. It was a year of record-breaking milestones, made possible by your generosity, dedication, and belief in our mission.

Thanks to you, we reached new heights. Our PHASE ONE Gala was the largest in our history, raising an incredible $1.2 million, while our FACT for PHASE ONE event sold out faster than ever, bringing in over $275,000. Your enthusiasm for these events didn’t just make them a success— it directly fueled our ability to fund critical, life-saving research.

And fund research we did. In 2024, PHASE ONE awarded more grants in a single year than ever before— five ground-breaking clinical trials launched under the leadership of world-class researchers, each targeting a different rare or aggressive cancer. These bold projects pushed the boundaries of innovation, accelerating progress for the patients who need it most.

Every step forward in cancer research starts with a bold idea, a dedicated researcher, and a community willing to invest in hope. Because of you, we continued to bridge the gap between promising ideas and real-world treatments, giving patients access to cutting-edge clinical trials that might otherwise never reach them.

As you read through this Annual Report, I hope you see the impact of your generosity reflected on every page. Your support is not just funding research— it’s creating possibilities, advancing treatments, and changing lives. Thank you for being an essential part of this journey.

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.

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.

The trial is currently open to enrollment­­– click here to learn more about eligibility.

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, they 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 combination therapy 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.

GRANT AMOUNT: $80,000

CANCER TYPE: Head & Neck Cancer

TRIAL PHASE: Phase II

Oral and oropharyngeal cancers often present at advanced stages, and traditional treatments such as surgery, radiation, and chemotherapy can result in significant morbidity and poor prognosis. The need for innovative and less harmful treatment options is paramount.

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.

Curcumin, derived from the rhizome of the Curcuma longa plant, has long been used in traditional Indian (Ayurvedic) and Chinese medicine for its medicinal properties. Curcumin, along with other curcuminoids found in turmeric, has been extensively researched for its anti-carcinogenic and chemopreventive effects.

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.

NOTCH-activated Adenoid Cystic Carcinoma (ACC) is a rare cancer that primarily affects the salivary glands in the head and neck. ACC poses significant treatment challenges due to its rarity, high rates of distant metastasis, and limited effective options for advanced cases.

While initially manageable through surgery and radiation, nearly half of ACC patients eventually face metastasis, and current treatments, including chemotherapy and immunotherapy, have shown limited clinical benefits, emphasizing the necessity of new therapeutic strategies for this difficult-to-treat cancer.

Dr. Hanna’s Phase I/II trial investigates 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 linked to shorter relapse-free periods and poor survival rates.

Preclinical data suggests synergy between Notch and CDK4/6 signaling. Building on this, Lenvatinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, known for its ability to block the formation of new blood vessels, has been included in the study based on evidence suggesting that it may counter ACC’s ability to foster tumor growth.

By exploring the combination of CB-103 with Abemaciclib or Lenvatinib and Abemaciclib alone, Dr. Hanna aims to leverage the potential synergies among these therapies, which could lead to improved treatment responses and progression-free survival rates.

As this research unfolds, it serves as a beacon of hope for patients and families impacted by NOTCH-activated ACC dealing with dire prognoses, and could potentially transform the trajectory of treatment for this rare and aggressive cancer.

Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is 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.

This condition can result in painful skin lesions, debilitating uterine fibroids, adrenal tumors, and aggressive kidney cancer, typically diagnosed in people during their 20s to 40s. Approximately 10-16% of those with HLRCC will develop kidney cancer, underscoring the urgent need for effective treatment methods.

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.

GRANT AMOUNT: $10,000

PROGRAM TYPE: Patient & Family Support

PROJECT FUNDED: 'Hope for the Holidays'

Walk With Sally (WWS) is a nonprofit organization dedicated to lessening the burden of cancer for children and families. Sadly, most of the children and families enrolled in WWS programs are living below the poverty line due to the many costs associated with cancer.

The end of year holiday period can be an increasingly challenging time for children in grief or survivorship trauma, as this is either the first holiday period without their parent or sibling, or they are painfully reminded that this may be their last.

The PHASE ONE Community Grant supported WWS’November Grateful Giving workshop which included licensed mental health professional guided animal and art therapy. WWS also provided holiday cheer through gifts and meals to 10 families of 4 in desperate need of support.

"We received gifts from your very lovely and generous foundation. It really made us feel good to be able to open some nice gifts from you. It warmed my heart and I really felt the love and holiday spirit. Especially since I am still fighting this cancer."
–Lisa M., WWS Program Recipient

LAUSD proposed a multi-pronged pilot in schools which includes the development and implementation of prevention education resources and media on cancer related to substance abuse.

Students will be informed on the relationship of cancer and drugs. The implementation will build skills and self-efficacy to delay or avoid the abuse of a substance like tobacco and cannabis that can have a negative effect on their bodies. Youth will also be linked to pre-intervention and intervention health services, such as screening, and treatment options.

"I am thrilled to collaborate with PHASE ONE on a project that resonates deeply with me. I have witnessed the tragic loss of friends to cancer linked to tobacco use, some of whom were young and had just embraced parenthood. Our students in Los Angeles navigate a landscape fraught with risks, and our goal is to empower them with knowledge so they can make informed and healthier choices throughout their lives." –Tim Kordic, LAUSD Health Education Programs Project Adviser

To learn more about past Community Grants PHASE ONE has funded, click the button below:

Insights from an Oncologist

What role do clinical trials play in cancer care, and why are they important to cancer research?
Clinical trials are the only way to advance scientific discoveries to improve patient outcomes, care and quality of life. At the heart of excellent cancer care is access to clinical trials.

What is the biggest misconception about clinical trials, and how do you help patients feel confident in enrolling?
The biggest misconception about clinical trials is that a new trial automatically ensures a better outcome than the current standard of care therapies. This is unfortunately not always the case. But, it is critical to perform clinical trials since, in some situations, they do open the opportunity for discovering better treatments.

From your perspective, what is the most exciting innovation in early-phase clinical trials right now, and how could it change the future of cancer treatment?
From my perspective, the most exciting innovation is applying personalized-precision oncology approaches to caring for patients and designing new clinical trials. We need to be thinking outside the box about individualization and molecularly guided therapies as opposed to a one-size-fits-all approach.

If you could share one message with patients and families about the importance of clinical trials, what would it be?
I think the most important message is that patients, families, and caregivers should inquire about clinical trials, but not be led to believe that all new drugs are always a panacea. Sometimes, repurposing old drugs in new ways can be incredibly effective in the right patient with the right disease.

A Patient's Perspective

What was it like to participate in a clinical trial, and how did it shape your cancer journey?
Being involved in a clinical trial was an easy decision for me. My trial offered the opportunity to receive immunotherapy and pin-point radiation prior to beginning treatment. I met with both UCLA and Cedars and both advised that the Cedars trial was the one to choose. You have more tests to undergo in a trial but you have great follow-up.

Can you share a moment from your trial experience that made you realize the impact of this research—not just for yourself, but for future patients?
After my trial was completed, the FDA approved the use of Keytruda the immunotherapy I received as standard of care for breast cancer. It made me happy that my inclusion in a Phase II trial will help other breast cancer patients for years to come.

What gave you the confidence to enroll in a trial, and what would you say to other patients considering one?
I gained confidence from meeting my oncologist and consulting with other physicians. I was patient 49 of 50 in a Phase II trial and knew that I would be receiving the medicine versus a blind trial. I would advise others to consult physicians to assist with their decisions. I was fortunate that I have a lot of doctors in my family and as close friends to call upon.

What do you wish more people understood about clinical trials and their role in advancing cancer treatment?
I wish more people realized that trials do not mean you are dying. Trials are used to obtain important data to help save and extend lives. In trials you really get to know your physician. You are paving the way for future patients so that one day we will live in a world free of cancer.