CHAPEL HILL - Based on proof-of-concept results from clinical trials at University of North Carolina Lineberger Comprehensive Cancer Center and Baylor College of Medicine, an investigational cellular immunotherapy for Hodgkin lymphoma has received a Regenerative Medicine Advanced Therapy designation from the U.S. Food and Drug Administration.
Tessa Therapeutics announced the designation based on preliminary clinical trial results for a chimeric antigen receptor T-cell (CAR-T) therapy studied in patients with relapsed or refractory Hodgkin lymphoma at UNC and BCM.
CAR-T therapy involves extracting specific immune cells from patients, engineering the cells in the lab to hunt tumor cells displaying a specific molecular target, and then re-infusing them back into the patient to fight their cancer.
In addition to optimizing the therapy through early clinical trials, UNC Lineberger researchers played a critical role in early laboratory studies that led to the design of the investigational therapy.
Tessa Therapeutics announced plans to continue developing the experimental treatment in phase II trials targeted for fourth quarter of this year.
"We started working on this therapy to improve outcomes for patients with relapsed or refractory Hodgkin lymphoma at a time when the prognosis for these patients was very poor, and the prolonged treatment was toxic, and impaired patients' quality of life," said UNC Lineberger's Barbara Savoldo, MD, PhD, professor in the UNC School of Medicine Division of Pediatric Hematology-Oncology and assistant director of the UNC Lineberger Clinical Immunotherapy Program. "Clinical data from the clinical trial we have conducted at UNC indicate the investigational therapy is safe, and response rates were remarkable in a heavily pre-treated population."
Under the direction of UNC Lineberger's Natalie Grover, MD, assistant professor of medicine and clinical director of the Cellular Therapy Program and UNC Lineberger's Anne Beaven, MD, associate professor of medicine and director of the Lymphoma Program, UNC Lineberger launched a phase 1b/2 clinical trial to study the safety of the CAR-T therapy for patients with relapsed or refractory Hodgkin lymphoma and for non-Hodgkin lymphoma positive for the CD30 cellular marker. BCM researchers independently launched trials of the investigational CAR-T therapy as well.
UNC Lineberger recruited Savoldo and Gianpietro Dotti, MD, now a UNC Lineberger member and professor in the UNC School of Medicine Department of Microbiology and Immunology, from BCM in 2015 to continue their work developing and studying novel translational CAR-T therapies, including the CD30 CAR-T therapy for lymphoma.
Savoldo led early laboratory studies at BCM that led to the development of the investigational therapy for CD30-positive lymphoma.
"Barbara's work designing the therapy was critical and was used in the trials at both institutions," said UNC Lineberger's Jon Serody, MD, Elizabeth Thomas Professor of Medicine, Microbiology and Immunology and director of the Cellular Therapy Program. "Our work was critical in coming up with a lymphodepletion approach that optimized the function of the therapy."
UNC Lineberger's results from the trial are pending publication, but researchers say preliminary data were promising, particularly when they used a specific chemotherapy regimen - known as a lymphodepletion - prior to infusion of the CAR-T cells.
"Most of the patients on trial had progressed on previous approved therapies," Grover said. "This treatment was well-tolerated, and these are patients who had really refractory disease."
The FDA designation is intended to expedite review of cell therapies designed to treat, modify, reverse or cure a series or life-threatening disease, and where preliminary clinical evidence has shown the drug has potential to address an unmet medical need.
UNC Lineberger is expected to be a site for the phase II trial.
In addition, UNC Lineberger researchers have launched additional clinical trials to expand and improve upon the investigational CD30-directed CAR-T therapy for lymphoma.
A clinical study has launched to investigate CD30-directed CAR-T immunotherapy for T-cell lymphoma that was supported by a grant from Stand Up To Cancer. Dotti and other researchers were named to the SU2C Meg Vosburg T-Cell Lymphoma Dream Team behind the effort.
In another clinical trial, UNC Lineberger researchers are working to improve CD30 CAR-T therapy for relapsed or refractory Hodgkin lymphoma using additional genetic engineering techniques to improve migration of the immune cells to the cancer.
An additional study will evaluate combination therapies, including immunotherapies known as checkpoint inhibitors, to improve responses for patients with relapsed or refractory classical Hodgkin lymphoma who progress on CD30-directed CAR-T immunotherapies.
"The majority of patients with Hodgkin lymphoma are cured with first-line therapy, but the prognosis is worse for patients who don't respond to initial therapy," Grover said. "We are working to try to improve the outlook for patients who don't respond to initial treatments."