Behind the DAD Trial: Sacituzumab Govitecan With EV in mUC

Bradley McGregor, MD, senior physician, clinical director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and instructor of medicine, Harvard Medical School, discusses background of the DAD trial (NCT04724018) which evaluated sacituzumab govitecan-hziy (Trodelvy) in combination with enfortumab vedotin-ejfv (Padcev) for the treatment of patients with treatment-resistant metastatic urothelial carcinoma.

The DAD trial is a single-center, open-label, nonrandomized phase 1 study which sought to assess the safety and efficacy of sacituzumab govitecan and enfortumab vedotin for patients with metastatic urothelial carcinoma progressing on platinum-based chemotherapy and PD1/L1 inhibitors.

Patients aged 18 years and older were eligible for enrollment if they had histologically documented confirmed predominant urothelial carcinoma, an ECOG performance status of 0 or 1, and measurable disease. While patients with squamous differentiation or mixed cell types were eligible for enrollment, those with small-cell carcinoma were not.

Transcription:

0:09 | So [when] we think about urothelial carcinoma, we know that antibody-drug conjugates, ADCs, play a critical role in the management. EV is available in the United States in this second-line setting based on a phase 2 trial showing improvement vs chemotherapy in the chemo, platinum, post-platinum and IO setting. We also know that sacituzumab govitecan was granted accelerated approval based on activity in a phase 2 trial. So both these drugs are available in the United States. They are both antibody-drug conjugates, they have unique toxicities, different payloads, different targets.

0:47 | We combine chemotherapy together, often, this is the basis for multiagent chemotherapy. But today actually, prior to our data, no trial actually looked at combining 2 different antibody-drug conjugates to be given simultaneously in any cancer. So given this idea, right, that we had different targets and payloads, non overlapping toxicities, there is really a rational idea that these drugs could be combined together. And that was the basis for the DAD trial that we presented at [the European Society for Medical Oncology] last year.