PHILADELPHIA (May 12, 2025) — Pooja Ghatalia, MD, Pan Associate Professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, has been granted funding from the Department of Defense (DoD) office of the Congressionally Directed Medical Research Programs (CDMRP) to study a new approach to treatment for patients with metastatic urothelial carcinoma.
The proposed intervention has the potential to improve treatment tolerance and quality of life for bladder cancer patients receiving highly efficacious but potentially toxic treatment that can cause debilitating side effects.
“It’s very exciting to see this study actually happen,” said Ghatalia. “At Fox Chase, our genitourinary group is really interested in looking at strategies that focus on the patient’s quality of life, minimize overtreatment, and potentially scale back on toxic therapies. Thanks to the DoD funding, that is what this study will do.”
Currently, first-line standard of care for patients with metastatic urothelial carcinoma is a combination therapy comprising the antibody drug conjugate enfortumab vedotin (EV) and the monoclonal antibody pembrolizumab (P). EV attaches to a specific protein on bladder cancer cells and delivers the chemotherapy directly inside the cells, and P, an immunotherapy agent, helps the patient’s immune system recognize and attack cancer cells.
While EV/P is effective, it also causes serious and sometimes permanent side effects, such as nerve damage, especially when given for extended periods. Bladder cancer patients typically receive EV/P until they can no longer tolerate the treatment’s side effects.
Therefore, Ghatalia and her team will use the $1.9 million in funding to pursue a single-arm phase II trial to evaluate a new approach to administering EV/P that could reduce these side effects. The team includes co-investigator Erin K. Tagai, PhD, MPH, an Assistant Professor in the Cancer Prevention and Control Research Program at Fox Chase, and Eric Ross, PhD, ScM, Director of the Biostatistics and Bioinformatics Facility.
In this trial, the researchers will test an initial induction phase of EV/P, which lasts about 18 weeks, followed by ongoing maintenance where the patient receives only P. They hypothesize that this induction-plus-maintenance approach could work as effectively as the current treat-to-toxicity model while lessening side effects and improving patient quality of life.
“The results of this study will provide clinicians with a valuable framework about whether it’s safe to stop enfortumab vedotin after six cycles and just continue pembrolizumab to get their patients a better quality of life,” said Ghatalia, who is also a member of the Nuclear Dynamics and Cancer Research Program.
The primary result the researchers are looking for is progression-free survival of 44% or better at 18 months, which would match the current EV/P standard. Patient quality of life will also be assessed using surveys that measure patients’ general health, bladder cancer symptoms, and treatment-induced nerve issues.
This study will also explore whether circulating tumor DNA (ctDNA), measured via blood draws at key timepoints during a patient’s progression through the trial, can predict treatment responses and outcomes. Retrospective analysis will help the researchers determine whether ctDNA might be used by clinicians in the future to guide when a patient can safely stop receiving EV.
The study, “Pembrolizumab Maintenance After Enfortumab Vedotin/Pembrolizumab Induction in Front-Line Metastatic Urothelial Carcinoma,” will be funded by the DoD CDMRP Fiscal Year 2024 Peer Reviewed Cancer Research Program Advancing Cancer Care through Clinical Trials Award. It is one of only five out of 51 such applications that have been awarded funding.