By Candace Gwaltney
April 16, 2026
IU plays significant role in FDA approval of new bladder cancer treatment
A new treatment for bladder cancer is transforming the outlook for patients, thanks in part to contributions by researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center.
Nabil Adra, MD, the Rikki and Leonard Goldstein Scholar in Cancer Research at the IU School of Medicine and a physician-scientist at the cancer center, is among the authors of results recently published in the prestigious New England Journal of Medicine from a multi-year clinical trial called KEYNOTE-905. The FDA approved the combination targeted therapy in November. With this new treatment regimen, a substantially higher percentage of patients with bladder cancer will be cured of their cancer.
“It's very inspiring to see something go from a Phase I study all the way to an FDA approval,” Adra said. “It’s even more inspiring when it's your patients that are being treated in the clinic and together, we see this transition over time from early studies — and then telling those patients that there's an FDA approval now.”
The decade-long path to approval started with an early-phase, multi-center Hoosier Cancer Research Network clinical trial that opened in 2015 with IU enrolling its first patients in 2016. Hristos Kaimakliotis, MD, associate professor in the IU School of Medicine Department of Urology, was heavily involved in the study and presented earlier findings at the 2019 American Urological Association Annual Meeting.
“It is gratifying to see the progress made over the last 10 years when we first opened the Phase I/II trial and started using immunotherapy in the pre-operating setting. This was based on the benefits seen in patients with advanced metastatic disease, and we were hopeful to see the same or similar benefits in an earlier stage with localized disease. The results were very encouraging,” Kaimakliotis said. “Since then, we have further combined antibody-drug conjugates to immunotherapy in the KEYNOTE-905 trial; the tremendous success led to its approval by the FDA and inclusion in the National Cancer Center Network guidelines.”
In total, 45 patients participated in the studies at IU: 27 patients enrolled during Phase I/II (with IU enrolling the highest number of patients in the study) and another 18 patients participated in the Phase III trial. The Phase III trial enrolled IU patients from 2019 to 2024.
The study treated bladder cancer patients who were ineligible due to other health issues or declined to receive chemotherapy.
“For those patients, it used to be that we would do surgery alone to remove the bladder and hope that the cancer does not recur,” Adra said. “But for the majority of those patients, the cancer would recur and ultimately cause death — so we had to do better.”
With the new bladder cancer treatment now available to patients, the field is rapidly changing. IU researchers are helping drive the next innovations in bladder cancer research.
One arm of the study received a combination of immunotherapy with pembrolizumab, plus targeted therapy called enfortumab vedotin, followed by surgery. The second arm of study participants received surgery only to remove the bladder.
Two years following treatment, the estimated event-free survival for patients who received the combination therapy followed by surgery was 74.7%, significantly higher than the 40% for those who received surgery only.
Adra was early in his career at IU when he first enrolled patients in the trial while an oncology fellow. A decade later, the treatment is changing how he treats bladder cancer.
“I have many patients still in my practice who were on the study and benefited a lot from this, and they are thriving, which is amazing,” Adra said. “And now I can give this regimen to new patients as standard care.”
The future of bladder cancer treatment
Tareq Salous, MD, assistant professor of clinical medicine at IU School of Medicine and a cancer center researcher, is the principal investigator for several bladder cancer clinical studies now open at IU.
Among the most promising studies is a bladder preservation trial that builds on the KEYNOTE-905 findings. Patients in the study receive the new combination therapy; if the treatment has a positive response with no evidence of cancer, the patient continues therapy without bladder-removal surgery (cystectomy).
“Taking the bladder out or doing cystectomy is a life-changing event for patients, so being able to save patients the need for that is wonderful,” Salous said.
This study is another Hoosier Cancer Research Network trial; IU is one of the few cancer centers enrolling patients nationally and is among the highest enrollers.
Salous notes that early results are promising with patients keeping their bladder and continuing to be cancer free.
Another trial open at IU could help patients who do require bladder removal for their cancer treatment. The MODERN trial uses circulating tumor DNA — cancer DNA detected in the bloodstream — to guide treatment after bladder removal. If cancer DNA is present, patients receive more aggressive therapy; if not, they may be able to forgo additional treatment.
“While we don’t yet have the results of many of these studies, I think the future is very, very promising for bladder cancer treatment as it’s moving away from traditional therapy to more of targeted therapies that cause less harm and better quality of life,” Salous said.
These and other clinical trials are offered thanks to a collaborative research team that includes Adra, Salous and Kaimakliotis as well as cancer center physician researchers in the Department of Urology and Division of Hematology/Oncology.
“It speaks volumes of our program and the collaboration between medical oncology and urology at the cancer center on these studies, which sets IU apart,” Adra said. “There's a lot of close collaboration for our patients — many of whom have complicated cases that require a lot of multidisciplinary care. Having that close collaboration not only in standard of care therapy, but even more importantly in research, makes a huge difference.”
