Dr. Berg on Key Ongoing Trials in Metastatic Urothelial Carcinoma

Stephanie A. Berg, DO, medical oncologist, Dana-Farber Cancer Institute, instructor in medicine at Harvard Medical School, discusses key ongoing trials in metastatic urothelial carcinoma (mUC).

Several trials are currently investigating treatment regimens for mUC in the first-line setting, Berg begins. The phase 3 EV-302 trial (NCT04223856) of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) aims to compare the efficacy of this combination vs standard-of-care (SOC) gemcitabine plus platinum-chemotherapy, Berg says. Patients enrolled in the study must have previously untreated locally advanced or metastatic urothelial cancer. Enfortumab vedotin received prior FDA approval for patients with locally advanced or mUC who had previously received platinum-based therapy and a PD-L1 inhibitor. Additionally, both enfortumab vedotin and pembrolizumab have been previously evaluated in combination and have shown favorable efficacy, Berg says.

The use of first-line chemoimmunotherapy combinations is also being investigated in the phase 3 NILE study (NCT03682068), Berg continues. This trial is an extension of the phase 3 DANUBE trial (NCT02516241) in unresectable, stage IV bladder cancer, which did not meet its primary end point of overall survival, she explains. The NILE study is comparing the efficacy and safety of durvalumab (Imfinzi) plus chemotherapy with or without tremelimumab (Imjudo) followed by durvalumab monotherapy vs chemotherapy alone in patients with unresectable, advanced mUC.

Furthermore, an investigational immunotherapy combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) or chemotherapy vs chemotherapy alone is also being evaluated in the phase 3 CheckMate901 trial (NCT03036098), Berg notes. Lastly, the ongoing phase 3 MAIN-CAV trial (NCT05092958) is currently assessing the addition of cabozantinib (Cabometyx) to the SOC immunotherapy avelumab (Bavencio) after chemotherapy in patients with mUC, Berg says.

Overall, these trials may help inform efforts to maximize the efficacy of these agents in the first-line or as maintenance therapy while still accounting for safety and tolerability, Berg concludes. All trials are currently open to enrollment.