Dr McGregor on the DAD-IO Trial in Treatment-Naive Metastatic Urothelial Carcinoma

Bradley McGregor, MD, senior physician, clinical director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and instructor of medicine, Harvard Medical School, discusses the rationale for the DAD-IO trial, which is an extension of the phase DAD trial (NCT04724018). DAD-IO will investigate the efficacy and safety of combination therapy consisting of sacituzumab govitecan-hziy (Trodelvy), enfortumab vedotin-ejfv (Padcev), and pembrolizumab (Keytruda) for the first-line treatment of patients with metastatic urothelial carcinoma.

In the original protocol for the DAD trial, investigators evaluated sacituzumab govitecan in combination with enfortumab vedotin in patients with treatment-resistant metastatic urothelial carcinoma. Previous results showed that the combination of the 2 antibody-drug conjugates elicited an overall response rate of 70% in evaluable patients (n = 23). McGregor notes that, more importantly, the combination was well tolerated, and the maximum tolerated dose was the standard full dose of both agents.

However, considering the potential for cumulative toxicities with the combination, the recommended phase 2 dose (RP2D) has been established at 7.5 mg/kg of sacituzumab govitecan and 1.25 mg/kg of enfortumab vedotin given on days 1 and 8 of each 21-day cycle. Notably, most patients treated in the first portion of DAD received prophylactic granulocyte-colony stimulating factor (G-CSF) at investigator discretion after 2 of the first 6 patients treated experienced neutropenic fever, McGregor says. In 16 of the 17 remaining patients who received G-CSF during cycle 1 of treatment, its addition to sacituzumab govitecan and enfortumab vedotin was well tolerated, he adds.

In the next portion of the study, DAD will continue to evaluate sacituzumab govitecan plus enfortumab vedotin at the RP2D in previously treated patients with metastatic urothelial carcinoma; DAD-IO will include patients with treatment-naive metastatic urothelial carcinoma who will receive sacituzumab govitecan plus enfortumab vedotin at the RP2D with the addition of pembrolizumab given at 200 mg once every 3 weeks for the first 6 cycles, then at 400 mg once every six weeks for up to 2 years.

The DAD and DAD-IO cohorts will each include 41 patients. The trial is expected to be activated in the near future to begin enrolling patients, McGregor concludes.