Dr Meric-Bernstam on the Efficacy and Safety of Dato-DXd in Metastatic Urothelial Cancer

“At a median follow-up of 10 months, we had not reached the median duration of response yet, and 76.2% of the patients at 6 months had ongoing responses. This is an exciting signal of activity. Notably, we’ve seen responses both from patients who have previously gotten enfortumab vedotin-efjv and those who have not, so this is quite an active agent.”

Funda Meric-Bernstam, MD, chair, the Department of Investigational Cancer Therapeutics–the Phase I Program, medical director, the Institute for Personalized Cancer Therapy (IPCT), the Nellie B. Connally Chair in Breast Cancer, the University of Texas MD Anderson Cancer Center, discusses updated efficacy and safety data from the ongoing phase 1 TROPION-PanTumor01 study (NCT03401385) evaluating datopotamab deruxtecan (Dato-DXd; Datroway) in locally advanced or metastatic urothelial cancer.

Results presented at the 2025 Genitourinary Cancers Symposium, showed that Dato-DXd had antitumor activity and manageable safety, with the majority of patients achieving disease control and durable responses, Meric-Bernstam begins. At a median follow-up of 10 months, the objective response rate (ORR) per blinded independent central review was 25% (95% CI, 12.7%-41.2%), the median duration of response was not evaluable (NE; 95% CI, 2.6-NE), and 76.2% (95% CI, 33.2%-93.5%) of patients maintained their response at 6 months. Notably, responses were observed in patients regardless of prior exposure to enfortumab vedotin-efjv (Padcev), indicating substantial activity in a heavily pretreated population, she adds.

The safety profile for Dato-DXd was consistent with prior reports and no new safety signals emerged, Meric-Bernstam continues. Distinctive adverse effects (AEs) more frequently associated with this agent than with other antibody-drug conjugates (ADCs) included mucositis or stomatitis, likely due to target expression in mucosal tissues, she notes. Hematologic toxicity was minimal, with only one case of grade 2 anemia reported, and no cases of neuropathy, Meric-Bernstam adds.

Interstitial lung disease (ILD) or pneumonitis remains a monitored concern with ADCs, Meric-Bernstam emphasizes. In this study, all pulmonary events underwent central review, and 2 cases of grade 2 and 3 ILD were reported, respectively. These findings underscore the need for ongoing vigilance regarding pulmonary toxicity; however, the incidence of these effects appears lower compared with other ADCs utilizing a similar drug payload, Meric-Bernstam states.

Overall, this agent demonstrates meaningful clinical activity and durable responses in a heavily pretreated patient population, Meric-Bernstam concludes.