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Dr McGregor on the Clinical Implications of the DAD-IO Trial in Urothelial Carcinoma

Bradley McGregor, MD, discusses the clinical implications of the DAD-IO trial in patients with metastatic urothelial carcinoma.

Bradley McGregor, MD, senior physician, clinical director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute; instructor, medicine, Harvard Medical School, discusses the clinical implications of the DAD-IO trial, which serves as an extension of the phase 1 DAD trial (NCT04724018), in patients with metastatic urothelial carcinoma.

DAD-IO aims to better understand the efficacy and safety of combination therapy consisting of sacituzumab govitecan-hziy (Trodelvy), enfortumab vedotin-ejfv (Padcev), and pembrolizumab (Keytruda) in the first-line setting in this patient population.

McGregor begins by stating that clinicians are particularly interested in the DAD-IO trial, though it’simportant to note that a press release published in May 2024 on the phase 3 TROPiCS-04 trial (NCT04527991), which compared sacituzumab govitecan with chemotherapy, revealed that the trial did not meet its primary end point for overall survival. Moreover, this press release raised concerns regarding thetoxicity of sacituzumab govitecan, he emphasizes. However, these data do not directly impact the DAD-IO trial, as DAD-IO uses a lower dose of sacituzumab govitecan, at 7.5 mg/kg compared with the 10-mg/kg dose that was explored in TROPiCS-04, according to McGregor. Furthermore, DAD-IO is being conducted in an earlier treatment setting and strongly encourages the use of Granulocyte colony–stimulating factor, McGregor notes. Despite the TROPiCS-04 results, McGregor believes sacituzumab govitecan could be a promising partner with enfortumab vedotin.

Looking ahead, if the DAD-IO trial demonstrates a response rate of approximately 75% to 80% with the addition of sacituzumab govitecan, it could generate significant enthusiasm for building upon the outcomes that the enfortumab vedotin plus pembrolizumab (Keytruda) combination has already achieved, he continues. The DAD trial data, which showed an objective response rate of 70% (95% CI, 47%-87%), albeit in a small sample (n = 23), are encouraging, he states. Anecdotally, patients have experienced durable responses on this therapy, and McGregor is hopeful that DAD-IO will allow researchers to replicate and expand on these successes.

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