OU’s Stephenson Cancer Center part of global trial

OU Health Stephenson Cancer Center at the University of Oklahoma Health Sciences Center participated in clinical trials that led to the approval of a new drug to treat uveal melanoma, a rare but deadly cancer of the tissues of the eye. Oncologist Alexandra Ikeguchi, M.D., who led Stephenson’s participation in the trials, is an author on a recently published article in the journal Nature Medicine that details the remarkable findings of the phase II trial.

The clinical trials tested a new drug, called tebentafusp, which was developed specifically for uveal melanoma. Unlike skin melanomas, which metastasize about 10% of the time, approximately 50% of uveal melanoma cases will spread, primarily to the liver. The new drug is genetically engineered to draw T cells into the metastatic tumor and prompt them to recognize a protein on the surface of the melanoma. That allows the cytotoxic T cells — one of the body’s “killer cells” — to attack the cancerous cells.

Results of the clinical trials showed a significant increase in survival for patients with uveal melanoma. Among participants in the phase II trial, all of whom had been previously treated for metastatic uveal melanoma, the median overall survival was 16.8 months. That’s more than double the median survival rate of 7.8 months for metastatic patients previously treated with a standard therapy. In the phase III trial, tebentafusp was tested as a first-line treatment for patients with uveal melanoma. In these patients, the median overall survival rate improved to 21.7 months.

“We started the trial with cautious optimism, but it ended up being even more successful than anticipated,” Ikeguchi said. “It’s very exciting to have a drug for the specific complexities of uveal melanoma.”

Ikeguchi’s work on the phase II trial yielded another important finding: Imaging the tumor with technologies like CT scans is not a good predictor of how successful the new drug is going to be. Rather, an analysis of the circulating tumor DNA provided a much more accurate picture. When researchers initially performed a CT scan of participants, the tumor appeared to be growing in 47% of those treated with the new drug. However, by testing the circulating DNA of the tumor, they saw an increase of cancerous cells in only 29% of patients, with 71% having some reduction. In addition, 12 patients had complete clearance of circulating tumor DNA, whereas no patients showed complete clearance through imaging scans. Researchers’ theory is that the CT scan captured the new T cells being pulled into the tumor by the drug, but couldn’t distinguish them from cancerous cells.

“This is the first therapy where that observation has been made,” Ikeguchi said. “The CT scan made it appear that the patient had not responded to the drug when they actually had responded quite well. This finding will create a shift in how we think as oncologists. As similar therapies become more prevalent, we shouldn’t rely solely on scans but consider other measures (like measuring the circulating tumor DNA).”

Participants in the clinical trials experienced some side effects with the new drug, namely rashes. However, those were easily treated and diminished as soon as the patient reached a stable dose. The drug, which was administrated through an IV, escalated in dose for the first three weeks before leveling out.

Uveal melanoma is relatively rare across the world. Ikeguchi said the United States has approximately 2,500 cases each year, and Western Europe sees a comparable number. The clinical trials testing tebentafusp included multiple sites in the United States, Canada, Germany, Spain, Australia and the United Kingdom.

Stephenson Cancer Center was chosen to participate in the trial in part because of its relationship with Dean McGee Eye Institute, also located on the campus of the OU Health Sciences Center. DMEI physician Brian Firestone, M.D., is an expert in ocular oncology and referred patients to the trial, Ikeguchi said.

“Not many academic health centers have someone with that specialty,” she said. “It allowed us to have the volume of patients so we could participate in the trial. We’re proud to be at the forefront of novel therapies, even for rare disorders like uveal melanoma.”

The U.S. Food and Drug Administration approved tebentafusp in January for the treatment of uveal melanoma. Although the initial escalating doses may need to be administered at an academic health center like OU Health, subsequent treatments can likely be administered by a community oncologist close to the patient’s home.