Findings from the phase 1/2 Duravelo-1 trial (NCT04561362) investigating zelenectidepevedotin (BT8009) in patients with metastatic urothelial carcinoma show promising results, particularly in those who are naive to enfortumab vedotin. The data, presented at the 2024 ESMO Congress, highlight the potential of this agent in a setting where treatment options are evolving.
The enfortumab vedotin-naive cohort of Duravelo-1 included patients with prior exposure to chemotherapy and immunotherapy. Among efficacy-evaluable patients (n = 38), the overall response rate (ORR) with zelenectidepevedotin was 45%, comprising 1 complete response (CR) and 16 partial responses (PR). The clinical benefit rate (CBR) was 61%. Among those with confirmed responses (n = 14), the median duration of response (DOR) was 11.1 months (95% CI, 3.9-not reached).
Comparing Nectin-4 Targeting Agents
Benjamin Garmezy, MD, assistant director, Genitourinary Research, Sarah Cannon Research Institute, noted the importance of understanding how to advance the development of zelenectidepevedotin, especially considering the existence of enfortumab vedotin, another Nectin-4–targeting drug with an MMAE payload. "How do we take this information [with zelenectidepevedotin] and move it forward, knowing that there’s another drug [for this disease, enfortumab vedotin], that’s a Nectin-4–targeting drug with an MMAE payload?"
Adverse Effect Profiles
A key factor in determining the role of zelenectidepevedotin will be evaluating its adverse effect profile in comparison to enfortumab vedotin. According to Dr. Garmezy, not all patients are suitable candidates for enfortumab vedotin, particularly those who experience neuropathy. Zelenectidepevedotin may offer an alternative for these individuals.
Ongoing Research
The phase 2/3 Duravelo-2 trial (NCT06225596) is currently underway, assessing zelenectidepevedotin as a monotherapy or in combination with pembrolizumab (Keytruda) in patients with locally advanced or metastatic urothelial cancer. Participants are either treatment-naive or have received at least one prior systemic therapy. This study aims to identify which patients benefit most from this therapy and to clarify the positioning of zelenectidepevedotin relative to enfortumab vedotin. Dr. Garmezy anticipates that findings from this trial will be integrated into the urothelial cancer treatment paradigm both in the United States and internationally.
