Astellas and Seattle Genetics unveiled data showing their antibody-drug conjugate shrank 44% of tumors and eliminated 12% of them in patients with advanced urothelial cancer. The treatment, enfortumab vedotin, could become an option for patients whose cancer has worsened despite receiving chemotherapy and checkpoint inhibitors.
The phase 2 data, presented Monday at the annual meeting of the American Society of Clinical Oncology (ASCO), come from 125 patients with urothelial cancer that has spread locally or metastasized elsewhere in the body. This cancer primarily occurs in the bladder, but it can also affect the urethra, kidneys and other organs in that part of the body. These patients are generally first treated with platinum chemotherapy.
“About half of the patients respond decently, but it’s a cumbersome, toxic chemotherapy regimen. About half of those patients relapse in about two years,” Clay Siegall, Seattle Genetics CEO, told FierceBiotech.
Doctors will then prescribe a checkpoint inhibitor, but these work for about 20% of patients, Siegall said, and they shrink tumors for about 11 to 12 months. There is no approved treatment for patients after checkpoint blockade stops working.
“Nobody is cured,” Siegall said.
The antibody piece of enfortumab targets the protein Nectin-4, which is found abundantly in 97% of urothelial tumors, according to ASCO. Its drug component disrupts the microtubule infrastructure—commonly called the railways of the cell and used for moving organelles around as well as to support the cell and give it shape.
Though 44% of patients logged enough tumor shrinkage to be called responders, Siegall said the waterfall plot of the data showed 84% of the patients saw some reduction in tumor size. Enfortumab also helped patients live a median 7.6 months longer and kept cancer at bay for about six months. The response rate was steady across patient subgroups, including those for whom PD-1/PD-L1 blockers did not work, those with liver metastases and those who had received three or more prior treatments.
“This consistency across subgroups demonstrates that there’s not just one group driving the overall benefit that we’re seeing,” said Andy Krivoshik, who heads up oncology at Astellas. And this consistency goes across trials, too.
“These phase II results replicate the phase I results very closely, which is not often the case in clinical trials,” said lead author Daniel Petrylak, M.D., a professor of medicine and urology at Yale Cancer Center, in the ASCO statement.
The study is enrolling a second group to see how enfortumab fares in patients too frail to undergo chemotherapy. And enfortumab is already in a global phase 3 confirmatory study comparing it to the doctor’s drug of choice, Siegall said, as well as a phase 1 study testing it earlier in urothelial cancer including as a frontline treatment in combination with chemo and/or checkpoint inhibitors.
Going earlier might allow for the elimination of the most toxic chemo drug or drugs from a patient’s regimen, or even to drop chemo altogether. But that will come after approval in relapsed patients. Astellas and Seattle Genetics are preparing an FDA submission, which they hope to file before the year is out.
And further down the line, the duo could expand their work into other cancers.
“We are exploring not only moving earlier in the disease continuum, but we’re also looking at other potential tumor types that have high Nectin-4 expression,” Krivoshik said. He kept mum on which tumors the partners might be interested in, but pointed to pancreatic, breast and lung cancers as possible targets based on the literature.
“We are learning from the trial and from biomarker data, and trying to understand the importance of Nectin-4 in other tumor types,” he said.