Smarter, Bolder Cancer Immunotherapy Clinical Trials

How the Parker Institute for Cancer Immunotherapy Translates Science for Faster Cures

At the heart of every Parker Institute clinical trial are patients. Holly Huntington knows this well, because she was once one herself.

“Breast cancer treatment was one of the hardest things I’ve ever gone through,” Huntington said. “I want to see cancer solved – and for me, that starts with following through on PICI’s clinical trials so that promising new treatments reach the patients that need them.”

At the Parker Institute, Huntington runs a small, mighty operations team that orchestrates clinical trials day-to-day. Whether its training clinic staff on data that should be reported or being the first point of contact for a physician who has a concern, Huntington’s team steps in to run the trial smoothly and ensure the study’s patients are cared for.

You need not look much further to find other PICI colleagues who are as deeply invested in cancer research. Some are physicians by training and others have spent their career advancing immunotherapy for cancer patients.

Executive director Justin Fairchild for example, is a veteran in the field. Prior to PICI, he worked on the teams that developed both ipilimumab and nivolumab, the first two immune checkpoint inhibitors approved by the FDA that changed the game for cancer patients. He now oversees PICI’s clinical science, data management, clinical operations and patient safety groups.

Fairchild explained, “What makes our team special is that we are diverse professionals with roots in academia, pharma and biotech. These varied backgrounds will help us bring innovative approaches to clinical trial execution.”

Clinical trials are the gold standard to evaluating a drug’s safety and efficacy. Unfortunately, they are slow. A new treatment will take around eight years, sometimes longer, from the time a cancer drug enters clinical trials until it is approved – if it ever is. They are costly, and they can often be redundant with competing trials studying the same drugs to treat the same cancers.

The Parker Institute tackles obstacles in clinical trials by removing inefficiencies to speed up the pace of study. From streamlining infrastructure that slows down approvals, to building innovative partnerships, to designing smarter studies, they invest resources in only the boldest, smartest science that can make a big impact on patients.

In three years, the team has grown its expertise to effectively run a trial from design to analysis. They’ve launched five clinical trials and funded a sixth in high-need areas. The first clinical trial they sponsored was in pancreatic cancer, a disease where only 8.5% of patients survive five years after diagnosis. The team charged ahead, undaunted.

Hacking pancreatic cancer

Before Robert Vonderheide, MD, DPhil, became an investigator of the Parker Institute, he studied a novel antibody called CD40 at the University of Pennsylvania. In mice, it had shown to activate an immune response in an extremely immunosuppressive environment, making it easier for checkpoint inhibitor immunotherapy to do its job. The data looked promising, but he didn’t have the partners or resources to bring it to trial.

Enter the Parker Institute.

Ramy Ibrahim, MD, who’s worked with the likes of Nobel Prize winner James Allison, PhD, Toni Ribas, MD, PhD, and Jedd Wolchok, MD, PhD, in the early development of checkpoint inhibitor immunotherapies, was gearing up an in-house clinical development team at PICI to take on this kind of trial. A bold trial that had strong scientific backing, it answered an important question for the field and could make a big impact for patients with limited treatment options.

Could targeting a protein called CD40 prime the tumor’s microenvironment to be receptive to immunotherapy and chemotherapy? Would the combination of four drugs lead to side effects or severe toxicities? It was the first time these questions would be explored in human pancreatic cancer.

With its collaborative model, the PICI team knew they were one of the few organizations that could build the synergies across the seven cancer centers in their network – not to mention, gather the right powerhouse partners across pharma, biotech and nonprofit, bringing in the likes of Cancer Research Institute, to make a trial like this happen.

Ibrahim assembled a specialized team to run the trial in-house, including a new head of translational medicine and regulatory affairs, Theresa LaVallee, PhD, who brought years of drug development experience.

Together alongside Dr. Vonderheide and other experts in the PICI network, they finalized the study while an internal team went to work behind the scenes. Rapid teamwork allowed the trial to go from concept to launch in only 6 months.

Ibrahim explains it would have been risky for a pharma company to open up a trial like this. However, “taking risks is part of our philosophy at the Parker Institute. We chose pancreatic cancer because it is difficult to treat and new treatments often have a high failure rate. We knew we could bring the right partners together and develop the right systems to tackle this challenge,” he said.

The expediency from the trial’s launch has continued with close collaboration of all partners. With PICI facilitating, the trial’s investigators, Bristol-Myers Squibb and Apexigen regroup bi-weekly to discuss patient safety and trial direction.

“Our investigators and partners make this clinical trial a priority. As a result of these meetings clinicians have identified and enrolled patients onto the trial ahead of what we expected,” said program manager of the trial Jaclyn Lyman. Speedy patient enrollment overcomes a common reason why clinical trials are often delayed, she explained.

Proof of the collaboration’s success is in the trial’s initial results, shared just a year and half after the first patient was enrolled in the study. An interim analysis, released at the 2019 American Association for Cancer Research meeting, revealed that the novel combination was able to shrink tumors in the majority of patients, with some responses lasting 10 months or more.

The trial is now recruiting patients for a Phase 2 study to further evaluate the combination’s efficacy. Equally meaningful, this model of boundary-breaking partnerships, rallied expertise and sophisticated technology has set the foundation for future forward-thinking trials.

Beyond the ordinary trial

Recently, the team launched a first-of-its-kind multi-center clinical trial that will focus on unearthing what biological markers can predict which patients will or will not respond to checkpoint inhibitors.

With this information, one of the first questions it seeks to answer is which patients will have a better response from getting one versus two checkpoint inhibitors. Why this question? A solo drug may work for some, but not all. And, two drugs may be more potent, but can come with worse side effects. Choosing correctly is key. Unfortunately there is little information that exists to guide treatment.

“This type of trial is a vision that I’ve had my whole career: using clinical trials to understand mechanisms,” commented Padmanee Sharma, MD, PhD, the trial’s lead at MD Anderson Cancer Center. “We’ve had some success, but we’re at the tip of the iceberg. More studies are needed to help define mechanisms and identify biomarkers.”

The team has taken a two-pronged approach to optimize the trial: they designed the trial to do deep analyses on just a few patients without foregoing its impact on a broad patient population. This means data can be gathered faster and insights extracted sooner. The team has also shortened bureaucratic processes by installing a centralized IRB (institutional review board) for the seven participating sites, trimming months off the clinical trial process.

IRBs play a crucial role to ensure patient safety at each research center, but they can also slow the work. With the centralized IRB, one lead IRB conducts the review and the six others agree to the decision, eliminating time lost on gathering individual approvals.

“Rather than taking weeks to have a patient consent form approved with each participating site’s IRB, the centralized IRB shortens the review to days,” said Jennifer Ayran, program manager on the trial.

Patients have been treated at MD Anderson Cancer Center and UCLA is enrolling patients, with more sites anticipated to open in the future.

What’s next

The Parker Institute will continue to investigate promising science with two more trials.

One trial advances recent breakthrough microbiome research from PICI investigator Jennifer Wargo, MD. With an assembly of top-notch partners, researchers will investigate whether altering the microbiome could improve a cancer patient’s response to checkpoint therapy.

“The trial is exciting because it tests innovative science that’s still very new to the field. We’re studying two complex biological materials donated from healthy patients in combination with immunotherapy. It’s truly cutting-edge,” comments Sultan Nawabi, who runs the trial’s operations.

Another trial takes a unique and efficient approach to study advanced prostate cancer. The Parker Institute intends to evaluate several combinations of experimental treatments in one efficient study using what’s known as a platform trial. The framework would mean new treatments could be evaluated with fewer patients, less time and a greater probability of success.

“A platform study allows us to be nimble. If one treatment arm doesn’t work well in patients, we’ll be learning why so that we can improve and iterate on the next one quickly, ”said Dr. Leo Nissola, the clinical scientist on the study.

Because this approach can be complex, few have tried it. But the Parker Institute team is equipped. They are passionate. And, they are gritty. It’s apparent in how they problem-solve together, debate vehemently and own their responsibilities, plus more.

Science first. Learn fast. Work together. Do it for the patients. The team breathes these values. Each study sheds new light on how immune therapies can be used to defeat cancer, and they are determined to accelerate progress. They have to, because lives are at stake.

Meet the Team

From data management to regulatory expertise, the team comes from rich and diverse backgrounds in academia, industry and pharma. Explore who they are.

Ramy Ibrahim | Chief Medical Officer and Vice President, Clinical Development

Describe your role

My primary role is to support and empower the clinical team to design, execute and deliver innovative clinical trials that generate robust data to inform the field and help cancer patients.

Why work in cancer?

As a medical oncologist, I have dedicated my career to help cancer patients. The work has been rewarding with advancements like immunotherapy that allow some patients to live longer, while also challenging as we still seek to understand why some patients don’t respond to immunotherapy. At PICI, patients are truly left, right and center.

Theresa LaVallee | Vice President, Translational Medicine and Regulatory Affairs

Describe your role

I have two roles at PICI. The first is to ensure PICI meets patients’ needs, safety and rights by adhering to FDA regulatory standards and rules. These steps are critical to progressing successful new drug treatment approaches beyond clinical trials to reach cancer patients. My second role is to assess biomarkers in clinical studies to scientifically understand why a drug treatment works or doesn’t work and what drugs a cancer patient should receive based on their tumor or immune system’s genomic or molecular makeup.

Why work for Pici?

I have spent my career trying to use science to get new medicines to cancer patients. I believe PICI has a recipe that will make a difference. We bring some of the smartest people together, collaborate with a wide range of institutions and use innovative technologies. We think and act “big.”

Jennifer Ayran | Clinical Program Manager

Describe your role

I oversee a clinical trial from the time we are developing the protocol through to study closure.

Why work in cancer?

We’re all in it together. Cancer affects so many people, and I believe the Parker Institute can make a change.

Ari Bitton | Senior Clinical Trial Manager

Describe your role

As a Clinical Trial Manager, my role is to support the day-to-day conduct of a clinical study, facilitating the research from concept or idea to execution. There are a number of logistics and relationships to track and manage, especially in such a highly regulated environment.

Why work for PICI?

At some point in our lives, it’s likely we will be impacted by cancer through a friend, loved one, colleague or even personally. This is my small way of making a contribution to a much bigger challenge. Working at PICI is a great opportunity to really put people and patients first. It’s also amazing that we get to work in such an incredibly collaborative, dynamic and cutting-edge research environment.

Julie Densmore | Clinical Scientist

Describe your role

I help evaluate the data that comes out of our human studies. I contribute to the strategic design of our clinical trials to make sure that we ask the right scientific questions, yield high-quality data, comply with the law and protect the safety of every participant.

Why work for PICI?

We have truly gathered the brightest minds together with the collective intention to tame the wild beast that is cancer. We are not beholden to the development of a product to sell or revenue to make; we are all bringing forward our unique expertise with the shared mission to improve lives.

Robyn Dobson | Project Manager

Describe your role

I help keep my team organized and focused. I work closely with the CMO and collaboration partners on bringing new trials to PICI. I also orchestrate think-tank like meetings with clinicians and scientists to inform PICI’s next study.

Why work in cancer?

I have lost and continue to lose loved ones to cancer. I’m in the fight as long as it takes to find a cure.

Justin Fairchild | Executive Director, Clinical Development

Describe your role

I work closely with the entire clinical development team to design and conduct clinical trials of novel immunotherapy combinations.

Why work in cancer?

I began my career working in the clinical trials office of a community cancer center and quickly found myself motivated to find more efficient and effective ways to execute oncology clinical trials. Having now worked on multiple cancer immunotherapies for 10+ years, I enjoy the challenge of finding new ways to increase the number of patients that benefit from these treatments.

Holly Huntington | Director, Clinical Trial Operations

Describe your role

I support clinical trials. The clinical trial concepts at Parker literally “spring” from the synergy created by the passionate collaboration of oncologist researchers. The level ground of our non-profit provides the unique environment, which facilitates and fosters this interaction, and provides the framework for moving a concept to an executable reality. My role is to lead the team responsible for bringing clinical trials “to life” at clinical trial sites, and then supporting the clinical sites throughout the trial life cycle.

Why work in cancer?

A lot of people I know have been sick with cancer and the side effects associated with treatment, including me. I want to help bring effective treatments with minimal unintended consequences to standard practice so that people who develop cancer in the future won’t have to be sick for very long.

Janelle Ibsen | Associate Director, Patient Safety and Pharmacovigilance

Describe your role

I ensure proper handling of safety data from PICI clinical trials and ensuring compliance with PICI processes and regulatory reporting requirements.

Why work for PICI?

The majority of my career has been in oncology and my passion to ensure the safety of cancer patients participating in clinical trials is what drives my motivation to work in cancer. PICI encourages collaboration, thinking outside of the box and, most importantly, puts patients as the highest priority during decision making.

Tiffany Lui | Clinical Trial Manager

Describe your role

I am responsible for coordinating and managing clinical study activities to meet the organization’s goals for clinical discovery. We are, in essence, at the forefront of where advancements in medicines are made. We can see what works, what doesn’t work and where we should be heading.

Why work for PICI?

Between the mission, collaborative structure, brilliant minds and a sense of urgency for breakthroughs, PICI is and will be a significant force in furthering new discoveries and innovations within cancer research. That, in itself, is something quite special and powerful to contribute to.

Jaclyn Lyman | Clinical Program Manager

Describe your role

As a Clinical Program Manager, I bring clinical trial concepts to life. I oversee the steps between the development of a clinical hypothesis, treatment of the first patients and eventually the analysis of what we learned and how the patients responded to treatment. In line with PICI’s mission, the aim is to treat patients faster by bringing together the right team and executing clinical trials as efficiently as possible.

Why work for PICI?

There was no other option in my mind; I had to work for PICI. PICI is committed and uniquely positioned to truly shifting paradigm; putting collaboration, science and patients at the forefront of everything we do. There is no greater joy than having the ability to help patients the way we do. I was fortunate to experience this first-hand at Memorial Sloan Kettering Cancer Center earlier in my career and now on a different scale through PICI.

Sultan Nawabi | Clinical Trial Manager

Describe your role

It is my job to ensure all groups participating are informed enough to execute the trial the way it is intended. This includes working with clinical sites, pharmaceutical companies, senior management, vendors, etc. My goal is to help anybody on my trial team get the job done safely!

Why work in cancer?

Why not? Cancer is one of the most prevalent and deadliest diseases. I want to be part of the collective that contributes to curing this devastating illness. Also, because cancer is not just one disease, working in cancer allows me to learn more and more about the body, genes, tumors and newly emerging treatments.

Leonardo Nissola, MD | Clinical Scientist

Describe your role

I wake up every day knowing that I’m part of the team that is moving the cancer immunotherapy field forward. Through collaboration, our team’s mission is to deliver novel research to hack cancer. We are here to make a difference in patient’s lives and to prevent others from becoming cancer patients, one clinical trial at a time.

Why work in cancer?

As a doctor, I have served cancer patients. It has changed me. Fighting cancer at the ground level changes the way you see life. It gives you a perspective; it puts you in your place; it shows you how frail it all is. I am grateful every day. I want to serve my community by finding a smarter way to treat cancer.

Theresa Samuel | Intern

Describe your role

As an intern, I am learning about clinical trials. I immigrated from Egypt, where I was a doctor. My medical background helps me review medical data and “speak the same language” as the primary investigators, who are also clinicians.

Why work in cancer?

I spent around 4 years in one of the biggest medical centers treating cancer in Egypt. I experienced the suffering of cancer patients and saw the challenges of curing the disease. All of it made me excited to work in immunotherapy, which I view as a new approach to make cancer a curable disease.

Leslie Staines-Valenzisi | Senior Clinical Trial Associate

Describe your role

I help activate the individual sites for each of our studies. I collect and maintain all regulatory documents; I create and track our Trial Master Files (TMF); and perhaps most importantly, I oversee the resupply and stock of the Investigational Medicinal Product (IMP) at each of the sites, in addition to the many other roles I play.

Why work for PICI?

The Parker Institute is one of a kind. Aside from our unique model, we have a group of brilliant individuals from various backgrounds coming together in a new and creative setting with the collective goal to understand and cure cancer. By encouraging our member sites to collaborate and share data, we enable the trial process to move faster and more efficiently.

Alvin Walters | Senior Clinical Data Manager

Describe your role

I manage the creation of the clinical database and collection of clinical data into that database for clinical trials.

Why work for PICI?

PICI is trying to make clinical trials more efficient and easier to start up and run. Having been in the industry for over 20 years, this fresh approach to running clinical trials was a welcome change to what I was used to in the pharmaceutical industry.

JingYing Xu | Clinical Scientist, Cellular Therapy

Describe your role

I translate cell and gene therapies from bench to bedside. Together with the clinical and research teams, I design, execute and deliver clinical trials that would help advance the field and help the patients.

Why work in cancer?

I have seen friends and family fighting for cancer, and I have seen people lose their loved ones to cancer. I want to do everything I can to help them. PICI is the place where the best scientists in the nation are given the resources to tackle the boldest research to help our patients. I am proud to be part of the team.