ESMO 2025 | Novel ADCs for bladder cancer beyond enfortumab vedotin

Standard of care in the first line is enfortumab vedotin and pembrolizumab. The new antibody drug conjugate has completely changed the landscape and the potency that they have, the impact in the long-term survival, the impact in the number of patients responding and achieving a complete response is double that we can expect with standard platinum-based chemotherapy. But novel agents are under development. We have agents, novel antibody drug conjugates, that are targeting HER2, HER3, DRD2 and others. And they are also in combination with immunotherapy, probably looking for some synergism. If we have biomarkers that we can use in daily practice, we will see that in phase three trials that are up and running. Probably the most advanced ones is the DV-001 in first line, trying to see the activity of Disitamab vedotin, a novel antibody drug conjugate targeting HER2, plus Pembrolizumab in the first line setting of patients expressing HER2. That would replace Enfortumab vedotin and Pembrolizumab. We will not see a direct head-to-head comparison in between EBP versus DV with Datopotamab deruxtecan and Pembrolizumab combination, but hopefully we will have a biomarker to try to select at least for those patients with expression of HER2. Novel agents targeting HER3, targeting DRD2 may be also useful at progression to Enfortumab vedotin or at progression to Datopotamab deruxtecan in the first line. Or maybe we can combine with chemotherapy, why not? So there are many trials up and running, many new antibody drug conjugates with different payloads, different targets, different strategies that may be good for patients in the sequential strategy and to identify, to classify, to try to tailor the systemic treatment of our patients in our clinics.

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