Dr Garmezy on Findings From the Duravelo-1 Trial in Metastatic Urothelial Carcinoma

“How do we take this information [with zelenectidepevedotin] and…move it forward, knowing that there’s another drug [for this disease, enfortumabvedotin], that’s a Nectin-4–targeting drug with an MMAE payload?”

Benjamin Garmezy, MD, assistant director, Genitourinary Research, Sarah Cannon Research Institute, discusses the phase 1/2 Duravelo-1 trial (NCT04561362) investigating zelenectidepevedotin (BT8009) in patients with metastatic urothelial carcinoma.

Findings from the enfortumabvedotin-ejfv (Padcev)–naive cohort of Duravelo-1 were presented at the 2024 ESMO Congress. This cohort included patients with prior exposure to chemotherapy and immunotherapy. Among efficacy-evaluable patients in this cohort (n = 38), the overall response rate with zelenectidepevedotin was 45%, including 1 complete response and 16 partial responses. The clinical benefit rate was 61%, which is an encouraging result from an early phase study, Garmezy says. Furthermore, the median duration of response was 11.1 months (95% CI, 3.9-not reached) among those with confirmed responses (n = 14).

These findings beg the question of how to further advance the development of zelenectidepevedotin, particularly given the availability of enfortumabvedotin in bladder cancer, Garmezy emphasizes. Both agents target Nectin-4 and have an MMAE payload. One key factor in this research will be to evaluate the adverse effect profiles of both agents, he notes. Not all patients are optimal candidates for enfortumabvedotin, especially those who experience neuropathy, he explains. Therefore, zelenectidepevedotin may be an alternative therapy for these patients, he states.

The ongoing phase 2/3 Duravelo-2 trial (NCT06225596) is evaluating zelenectidepevedotin as monotherapy or in combination with pembrolizumab (Keytruda) in patients with locally advanced or metastatic urothelial cancer who are either treatment naive or have received at least 1 prior systemic therapy. This study will identify which patients benefit most from this therapy, as well as which patients could receive either zelenectidepevedotin or enfortumabvedotin, Garmezy reports. In the future, findings from this trial should be integrated into the evolving urothelial cancer treatment paradigm in both the United States and international settings, Garmezy concludes.