Initial results from the TROPION-PanTumor03 phase 2 trial, presented at the 2025 ESMO Congress, show that the combination of DATROWAY® (datopotamab deruxtecan) and rilvegostomig offers significant tumor responses and disease control in patients with locally advanced or metastatic urothelial (bladder) cancer, a population with limited treatment options and poor long-term survival.

According to Business Wire, DATROWAY is a TROP2-directed antibody drug conjugate (ADC) co-developed by Daiichi Sankyo and AstraZeneca, while rilvegostomig is AstraZeneca’s PD-1/TIGIT bispecific antibody, designed to enhance immune response against tumors.

Key Findings from the Trial

In a sub-study of 40 patients, DATROWAY plus rilvegostomig was evaluated as both first- and second-line therapy:

• First-Line (n=22; cisplatin-ineligible, untreated):
  • Objective Response Rate (ORR): 68.2%
  • Disease Control Rate (DCR): 95.5%
  • Median Progression-Free Survival (PFS): Not reached; 73.5% PFS at 12 months
    These results suggest robust tumor shrinkage and disease stabilization in newly treated patients unable to receive standard cisplatin chemotherapy.
• Second-Line (n=18; prior platinum chemo, no immunotherapy):
  • ORR: 38.9%
  • DCR: 83.3%
  • Median PFS: 12.5 months; 60% PFS at 12 months
    Even in patients whose disease progressed after platinum-based chemotherapy, the combination showed meaningful activity.

Median duration of response was not reached in either group at the time of analysis, indicating the potential for long-lasting benefit.

Safety Profile

The safety of DATROWAY plus rilvegostomig was consistent with known profiles for each drug. Grade 3 or higher treatment-related adverse events occurred in 18.2% (first-line) and 38.9% (second-line) patients, most commonly increased amylase, neutropenia, and (less frequently) stomatitis, decreased appetite, and anemia. Notably, interstitial lung disease (ILD) was infrequent and did not reach grade 3 or higher severity.

Clinical Impact and Next Steps

Given the five-year survival rate for metastatic urothelial cancer is less than 10%, these findings mark a significant advance. Dr. Sun Young Rha of Yonsei Cancer Center emphasized that the high disease control rate in first-line settings highlights the potential of this combination, warranting broader investigation.

To further evaluate this approach, the TROPION-Urothelial03 phase 2/3 trial has been initiated, comparing DATROWAY plus platinum-based chemotherapy to current standards in previously treated metastatic urothelial carcinoma.

Conclusion

DATROWAY plus rilvegostomig demonstrates promising efficacy and a manageable safety profile in both first- and second-line settings for metastatic urothelial cancer. These results support ongoing pivotal trials and represent hope for improved outcomes in a patient group with significant unmet needs.