Predicting Responses to Sacituzumab Govitecan Combo in Urothelial Cancer

In a conversation with CancerNetwork^® at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Bradley McGregor, MD, spoke about potential subgroups of patients with urothelial carcinoma who may benefit from regimens containing sacituzumab govitecan-hziy (Trodelvy) and enfortumab vedotin-ejfv (Padcev) as part of the DAD trial (NCT04724018).

McGregor is the director of Clinical Research for the Lank Center of Genitourinary Oncology and a medical oncologist specializing in genitourinary malignancies at Dana-Farber Cancer Institute.

Following initial reports of favorable safety and responses with sacituzumab govitecan plus enfortumab vedotin in this trial in progress, investigators amended the DAD study to include 2 cohorts consisting of distinct populations. One cohort will explore continued treatment with the combination (DAD), and another will assess the doublet in combination with pembrolizumab (Keytruda) in patients who are treatment-naïve (DAD-IO).

McGregor highlighted that the next steps for research may involve conducting spatial analyses to determine factors beyond Nectin-4 and Trop-2 that potentially influence a patient’s probability of responding to these regimens. Additionally, he said he hopes to achieve early and enduring disease control across this patient population.

Transcript:

When we think about the antibody-drug conjugates, the thought is that Nectin-4 and Trop-2 are universally expressed. In urothelial carcinoma, we don’t need to test for them, and so we don’t have any biomarkers; we usually [use] one or the other. That is something we want to look at. We’re trying to look at some of the staining for Nectin-4 and Trop-2 and [doing] spatial analysis to see if there are other factors that can maybe predict who responds or doesn’t respond. It may be both, or one.

Realistically, I will tell you that in the DAD study, we had patients up to the age of 83 years [who] were in this trial. This was not a trial of just 50- and 60-year-old [patients], and [treatment] was well tolerated with appropriate management. Finding the right patient reach will be important. But ultimately, bladder cancer is a very aggressive disease. If we can control more cancer earlier, that’s going to benefit our patients. My hope is not only to control cancer earlier but get durable control. That is something we hope we can do for our patients with bladder cancer.

Reference

McGregor BA, Kwak L, Sonpavde GP, et al. Sacituzumab govitecan (SG) plus enfortumab vedotin (EV) for metastatic urothelial carcinoma (mUC) treatment-experienced (DAD) and with pembrolizumab (P) in treatment naïve UC (DAD-IO). J Clin Oncol. 2024;42(suppl 16):TPS4618. doi:10.1200/JCO.2024.42.16_suppl.TPS4618