A recent study presented at the 2025 ESMO Congress has revealed that the combination of datopotamab deruxtecan-dlnk (Dato-DXd) and rilvegostomig shows significant antitumor activity in patients with locally advanced or metastatic urothelial cancer. The findings are particularly relevant for those who are cisplatin-ineligible or have been previously treated with platinum-based therapies. This data comes from cohort 6B of the phase 2 TROPION-PanTumor03 trial (NCT05489211).
In the first-line treatment cohort of 22 patients, the confirmed objective response rate (ORR) was an impressive 68.2% (95% confidence interval, 45.1%-86.1%). The disease control rate (DCR) over 12 weeks reached 95.5% (95% CI, 83.4%-99.5%). Patients experienced a median time to response of 1.4 months, and although the median duration of response (DOR) was not calculable, data suggested it was significant, with a lower limit of 9.4 months.
The study also analyzed a second-line therapy cohort comprising 18 patients. In this group, the confirmed ORR was 38.9% (95% CI, 17.3%-64.3%), with a DCR of 83.3% (95% CI, 66.6%-93.7%). The median time to response was 1.3 months, while the median DOR remained not calculable.
Dr. Sun Young Rha, the lead author and professor of medical oncology at the Songdang Institute for Cancer Research at Yonsei University College of Medicine, emphasized the importance of these findings. He stated, “The combination of Dato-DXd plus rilvegostomig demonstrated promising efficacy in patients with locally advanced or metastatic urothelial cancer who were cisplatin-ineligible and patients who had progressed on prior platinum-based chemotherapy.”
Despite advancements in treatment options, there remains a critical need for effective therapies for this patient population. Dato-DXd is classified as a TROP2-directed antibody-drug conjugate (ADC), while rilvegostomig is a bispecific IgG1 antibody targeting PD-1 and TIGIT receptors.
The TROPION-PanTumor03 trial is an open-label study evaluating Dato-DXd, either as a monotherapy or in combination with other anticancer agents, for patients with advanced or metastatic solid tumors. Participants enrolled in the trial had to meet specific criteria, including having histologically confirmed, unresectable, locally advanced or metastatic urothelial cancer without prior exposure to certain treatments.
Patients in the first-line cohort were required to be cisplatin-ineligible and had to have an Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2, along with other health criteria. The median age in this cohort was 71 years, with a majority being male (77.3%) and most having AJCC stage IV disease (86.4%). In contrast, the second-line cohort had a median age of 66 years, with similar gender and disease stage distribution.
The trial’s primary endpoints focused on the investigator-assessed ORR per RECIST 1.1 criteria, alongside safety and tolerability metrics. Secondary endpoints included DCR, DOR, and progression-free survival (PFS). In the first-line cohort, the median PFS was not calculable at a median follow-up of 10.8 months. The 6- and 12-month PFS rates were reported at 85.9% (95% CI, 62.4%-95.2%) and 73.5% (95% CI, 46.5%-88.4%), respectively. The second-line cohort reported a median PFS of 12.5 months (95% CI, 4.2-NC) with 6- and 12-month PFS rates of 72.2% (95% CI, 45.6%-87.4%) and 60.0% (95% CI, 33.7%-78.7%).
Treatment-related adverse effects (TRAEs) were noted, leading to dose reductions in 63.6% of patients in the first-line cohort and 22.2% in the second-line cohort. Interruptions occurred in 45.5% of the first-line patients and 33.3% of the second-line group. Discontinuation rates were 9.1% and 16.7%, respectively. Dr. Rha confirmed that the safety profile of Dato-DXd and rilvegostomig was consistent with prior reports, without new safety signals emerging.
Adverse effects of particular interest for Dato-DXd in the first-line group included oral mucositis/stomatitis (40.9%), ocular surface events (18.2%), and drug-related interstitial lung disease/pneumonitis (4.5%). For rilvegostomig, notable adverse effects included hepatic events (13.6%) and dermatitis/rash (50.0%).
In the second-line cohort, the incidence of oral mucositis/stomatitis was notably higher at 61.1%, with other adverse effects presenting similarly. The study highlighted that stomatitis, nausea, asthenia, and fatigue were among the most commonly reported TRAEs across both cohorts.
In conclusion, Dr. Rha underscored the significance of these results, asserting that further exploration of Dato-DXd in combination with rilvegostomig in first-line settings for locally advanced or metastatic urothelial cancer is warranted. The research findings contribute to the growing body of evidence aimed at improving treatment outcomes for this challenging patient population.
Dr. Rha disclosed consulting and advisory roles with multiple pharmaceutical companies, including Amgen, Astellas Pharma, and AstraZeneca, among others. These disclosures are essential to consider for transparency regarding potential conflicts of interest in the study’s findings.
