- The targeted therapy enfortumab vedotin produced responses in 44% of patients with locally advanced or metastatic forms of urothelial cancer who had been previously been treated with platinum chemotherapy and a PD-1 or PD-L1 immune checkpoint inhibitor.
Why this matters
- Urothelial cancer progresses in 75%-80% of people with advanced disease who receive an immune checkpoint inhibitor.
- There is no remaining approved standard-of-care treatment option for postimmunotherapy progression.
- Enfortumab vedotin is an antibody-drug conjugate that targets a protein highly expressed in urothelial cancers.
- Phase 2 trial of 125 patients with locally advanced or metastatic urothelial cancer previously treated with a PD-1/L1 inhibitor and platinum-based therapy.
- Patients received 1.25 mg/kg intravenous enfortumab on days 1, 8, and 15 of each 28-day cycle.
- Funding: Seattle Genetics; Astellas Pharma.
- 44% of patients achieved a confirmed overall response rate (ORR):
- Complete response: 12%.
- Partial response: 32%.
- Stable disease: 28%.
- Progression: 18%.
- Not evaluable: 12%.
- Median PFS, 5.8 (95% CI, 4.9-7.5) months.
- Median duration of response, 7.6 (range, 0.95-11.30+) months.
- Median OS, 11.7 (95% CI, 9.1-not reached) months.
- 41% of those whose cancers had not previously responded to a checkpoint inhibitor responded to enfortumab.
- 38% of those with cancer metastasized to the liver responded.
- Most common grade 3 or higher treatment-related adverse effects were neutropenia (8%), anemia (7%), and fatigue (6%).
- Single-group design.
- "I'm compelled by this data," said ASCO expert Robert Dreicer, MD, from the University of Virginia School of Medicine in Charlottesville. "The median survival approaches a year, and while it’s a phase 2 study, the reality is that front-line chemotherapy is the best we have, and the median survival is 13 months. I look at this data as effective therapy, and I would support accelerated approval."