Moffitt Cancer Center’s Clinical Trials Focus on Expansion, Diversity and Innovation
When Branden Akens was driving home from his annual checkup with his oncologist in 2015, he had a bad feeling.
He had been in remission for about four years after being diagnosed with acute lymphoblastic leukemia (ALL) his senior year of high school. His life was back on track and he was working toward a degree in graphic design. But something felt off.
His feelings were confirmed when he received a phone call before he could even make it back to his Orlando home. It’s not great, doctors told him. His cancer was back.
Now an adult, Akens was referred to Moffitt Cancer Center where he underwent a bone marrow transplant. Although the transplant was successful, his cancer returned for a third time a few years later. Doctors gave him two choices: more chemotherapy followed by a second bone marrow transplant or enrollment in a clinical trial using a new cellular immunotherapy called chimeric antigen receptor T-cell therapy, or CAR T.
CAR T involves taking a patient’s own T cells and genetically modifying them to recognize and destroy cancer once they are infused back into the body. While CAR T had been approved for children with acute lymphoblastic leukemia at the time, this trial was investigating whether CAR T could be used to successfully treat adults with the disease.
“I looked into the trial and at this point I was all in,” Akens said. “There’s no reason not to try it if I am eligible and it’s being offered to me. This seemed like the most feasible chance for a cure.”
Activating Trials
Moffitt’s vision is to create revolutionary breakthroughs and innovations that rapidly impact and save more lives.
“What we do best is treat the current patients with optimal therapies, but we are also always thinking about pushing the field forward so that tomorrow’s patients can get even better therapies,” said Patrick Hwu, MD, president and CEO of Moffitt and a world-renowned researcher in tumor immunology.
In order to find new treatments for patients, Moffitt relies on its robust network of research studies. The cancer center offers one of the largest portfolios of clinical trials in the nation, with nearly 400 active treatment trials, over 1,200 patients accrued annually and 13,000 treatments provided per year.
Clinical trials, or interventional studies, investigate the efficacy and safety of a new treatment or combination of treatments not yet approved by the U.S. Food and Drug Administration (FDA). During fiscal year 2022, Moffitt opened more than 200 new interventional studies across its campuses.
Many clinical trials involve cellular therapies, which improve a patient’s ability to fight cancer by collecting and modifying certain cells that make up the immune system before infusing them back into the patient. This includes CAR T and tumor-infiltrating lymphocyte, or TIL, therapy, which extracts immune cells present inside tumors, grows billions of them in the lab and then infuses them back into the patient to attack the cancer. Among the examples of cellular therapy trials:
- CAR T for adults with acute lymphoblastic leukemia — The trial Akens was on investigated the use of CAR T in adults whose ALL failed to respond to standard therapies. The phase 1 and 2 trial, led by medical oncologist Bijal Shah, MD, resulted in FDA approval of the treatment now called TECARTUS® in the fall of 2021.
- CAR T for relapsed multiple myeloma — There is no cure for multiple myeloma, which can be deadly for patients who have relapsed after multiple therapies. Thanks to an international trial in March 2022, the FDA approved CAR T for adults with multiple myeloma who are not responding to treatment or whose disease has returned. Melissa Alsina, MD, head of the Multiple Myeloma Section in the Blood and Marrow Transplant and Cellular Immunotherapy Program, led the phase 2 trial at Moffitt.
- TIL for non-small cell lung cancer — A research team led by thoracic oncologist Ben Creelan, MD, conducted a first of its kind pilot study among 16 Moffitt patients with metastatic non-small cell lung cancer. TIL reduced tumor size in most patients, and two patients had a complete response to the treatment.
- CAR T for ovarian cancer — Researchers led by Robert Wenham, MD, chair of Moffitt’s Gynecologic Oncology Program, and José Conejo-Garcia, MD, PhD, chair of Moffitt’s Immunology Department and co-leader of its Immuno-Oncology Program, have launched a CAR T trial for patients with recurrent ovarian cancer. Conejo-Garcia’s lab has created a CAR that introduces follicle-stimulating hormones (FSH) into T cells. The genetically modified CAR T cells can then seek out and destroy cancer cells expressing an FSH receptor protein found on a large number of ovarian cancer cells.
- Cellular therapies for other solid tumors — While TIL is expected to be approved by the FDA for melanoma later this year, cellular therapies are still being investigated in other solid tumors. Moffitt is studying CAR T and TIL in HPV-related head and neck cancer, bladder cancer, penile cancer, kidney cancer, breast cancer and sarcoma.
Another important leg of Moffitt’s clinical trial portfolio are precision medicine trials, which tailor individualized therapies for a specific patient using information such as tumor mutations and biomarkers. For example, Eric Haura, MD, associate center director of Clinical Science, and his team are looking at ways to target RAS, proteins that are frequently mutated in cancer. RAS mutations can be found in melanoma, lung, pancreatic, colon and other gastrointestinal cancers, and preparation is underway to open phase 1 trials in the coming months.
The cancer center is also leading the way in nontherapeutic, or observational, studies, such as Moffitt’s COVID-19 study. Led by Anna Giuliano, PhD, founding director of the Center for Immunization and Infection Research in Cancer Program, and Jeffrey Lancet, MD, chair of the Malignant Hematology Department, the study investigated if cancer patients had a response to the Moderna COVID-19 vaccine and if that response differed by diagnosis and treatment. The results, published in JAMA Oncology, showed 71.3% of patients developed antibodies after the first dose and 90.3% after the second. However, patients with blood cancers had lower antibody rates (84.7%) when compared with those with solid tumors (98.1%).
Harnessing Innovation
As trial infrastructure expands, the Clinical Trials Office will build in new ways to speed up trial activation and increase efficacy when it comes to matching patients to trials.
“We all know patients who have benefited from therapies, but we also know those who did not benefit because we did not get trials activated in a timely way,” Haura said.
Scientists in Dr. Eric Haura’s lab are looking at ways to target RAS, proteins that are frequently mutated in cancer.
Innovation and digital technologies will play a vital role in ensuring no patient misses out on a trial they are eligible for. Pilot efforts are underway testing a clinical trial matching software that uses artificial intelligence (AI) to sift through large amounts of information, including electronic medical records and molecular data, to help enroll patients. The software is part of the cloud-based Moffitt Cancer Analytics Platform, or MCAP, and thanks to a $2 million federal grant to support AI in cancer research, MCAP will continue to grow.
“Collecting and processing all that information is increasingly becoming much more complex than it used to be, so we need to leverage technology, AI and precision medicine to come up with cutting-edge ways to treat patients in our catchment area and beyond,” said Hatem Soliman, MD, medical director of the Clinical Trials Office.
When it launched in 2018, Moffitt STAR — a 170-gene panel that looks at changes in both tumor DNA and RNA — made it easier than ever to use a patient’s unique genetics to match them to a targeted therapy or trial. Moffitt pathologists and scientists are now looking to expand the panel to analyze 500 genes, increasing the chance of matching patients to trials. Validation studies are underway, and the team is hoping to launch the new assay in late 2022.
Moffitt’s pathology team has also developed a new tool to help enroll patients in clinical trials. Haura secured funding from the Salah Foundation and initiated work on the RNA STEP, or Salah Targeted Expression Panel. The panel, which was built over the past two years, extracts mRNA from tumor samples and looks for changes in mRNA expression for 204 different genes. If the expression is higher for the FSHR gene, for example, a patient might be more likely to respond to CAR T cells that target FSHR on cancer cells. The panel is currently being used to match patients to the ovarian CAR T trial and will next be tested on lung cancer samples.
Moffitt also has plans to expand its early phase therapeutics program, typically called the phase 1 program. This will help bring more innovative medicines to the cancer center and better tailor treatments to patients.
“The things we learn about tumor biology in our research laboratories, like mutations in some genes that drive cancer growth, show us what we need to develop a drug against,” Haura said. “A lot of early phase therapeutics are going right after the patient population based on gene mutations or other biomarkers. We need to invest in expanding our phase therapeutics program to be more streamlined and to partner with the industry better so we can activate studies faster, accrue faster and be able to do these precision medicine studies.”
Currently, Moffitt is working to recruit a new program leader for early therapeutics and hire dedicated phase 1 faculty. The cancer center is also looking into building out more clinic space.
Expanding the Portfolio
The research institute is still navigating the effects that the COVID-19 pandemic had on cancer research around the world, as well as new challenges like staffing and a changing job market. But the ultimate goal is to continue to grow and scale up research efforts, especially as Moffitt continues to open new locations.
“The clinical trial infrastructure is trying to chart out a vision for growing alongside the institution in order to fulfill its mission of providing cutting-edge therapies, with a particular emphasis on novel therapies like immunotherapy and cellular therapy,” Soliman said. “That is a strong focus at Moffitt and hopefully one that will make us more of a mecca for people coming to get those kinds of treatments.”
Over the past year, Moffitt has been able to leverage increasing clinical trial activation with its expansion efforts. Five studies opened at Moffitt at Wesley Chapel and eight at Moffitt at International Plaza spanning multiple disease sites.
Moffitt at International Plaza’s hybrid infusion center offers treatments for both standard of care and trial patients.
In November 2021, Moffitt at International Plaza opened an investigational laboratory space capable of handling research samples and began offering infusion treatments for certain clinical trials, creating a hybrid infusion center that can treat both standard of care and trial patients. This eliminates the need for a separate Clinical Research Unit, like at the Magnolia and McKinley campuses, and fosters a more creative use of space. Moffitt at International Plaza also opened a new Cold Cap Lounge to not only offer the hair loss prevention service to patients, but also provide additional infusion and waiting space when needed.
The hybrid space has proved successful at the International Plaza location and is a great model on how to best use space as Moffitt continues to expand into areas such as south Hillsborough County and Pasco County.
“We are hoping what we can do is create a network of sites and main centers to be able to quickly coordinate where a potential trial of interest would be open for a patient and direct their care to the appropriate facility to get them access to care when they need it,” Soliman said.
If patients must go to the clinic on the Magnolia campus for a certain trial infusion treatment, they could still potentially go to a satellite location in their community for things like blood transfusions and scans. This can help ease some of the stresses of cancer, such as travel and treatment time, and can help accomplish Moffitt’s goal of getting patients the right care where and when it’s most convenient for them.
Tackling Health Disparities
As clinical trials continue to grow, it’s important to ensure enrollment in those trials is reflective of Moffitt’s catchment area — 23 counties spanning West Central Florida where 86% of Moffitt’s patients live — and that trials offered are relevant to communities with a disproportionate burden of the disease. If trial enrollment is not diverse, new treatments cannot be broadly applied to all groups.
According to the Sidney Kimmel Comprehensive Cancer Center, less than 10% of patients with cancer who are enrolled in clinical trials are racial or ethnic minorities. From 2016 to 2018, 5.4% of patients enrolled in clinical trials at Moffitt were Black and 8.7% were Hispanic.
There are multiple factors that contribute to health care disparities. For some, there are socioeconomic issues such as transportation, child care and lack of access to affordable insurance. For others, it’s mistrust that is deeply rooted in the nation’s history of bias and betrayals such as the Tuskegee Experiment.
To help address these disparities in trials, the cancer center has appointed medical oncologist Kedar Kirtane, MD, as the new physician director for clinical trials – community outreach.
“The biggest first step is making sure we are engaging local organizations and working with groups entrenched in those communities to figure out what we can do better,” Kirtane said. “Part of the problem is not knowing what we can do better, and we can only find that out by talking to local groups.”
Kirtane plans to use an institutewide survey of Moffitt providers, clinical trial coordinators and other clinical trial personnel to assess their ideas to better understand the barriers to enrollment and strategies for improvement. He will also chair the Reaching and Engaging Special Populations to Expand Clinical Trials Committee, which brings together a broad coalition of disparities researchers, community activists and clinical trial leaders at Moffitt in order to advocate for a wider representation of underrepresented groups in clinical trials.
“Disparities are becoming more and more prominent as part of the national discourse,” Kirtane said. “We have a really strong group of people who are already interested in this work and trying to do a better job to make sure the vision is singular and everyone is collaborating effectively.”
Keeping the Ball Rolling
Not only did patient Branden Akens’ involvement in a clinical trial help lead to the FDA approval of CAR T for adults with acute lymphoblastic leukemia, but it has also kept him in remission for five years.
During that time, he has gotten married, finished college and bought his first home. All things he says he doesn’t know if he would have been able to do if it wasn’t for a clinical trial.
During their time in the hospital, Crystal Akens folded 1,000 paper cranes as a wish for good health for Branden. In Japanese culture, it is believed that anyone who folds 1,000 origami cranes will be granted a wish by the gods.
“This is life and death for a lot of people,” he said. “For people who don’t have a lot of other options, it’s a matter of getting trials to them and bringing visibility to them. I think having more accessibility is always a better thing. Hopefully the ball keeps rolling and more people can get the help they need.”
