DATROWAY® Plus Rilvegostomig Demonstrates Promising Tumor Responses in Metastatic Urothelial Cancer in TROPION-PanTumor03 Phase 2 Trial
Initial results from a sub-study of the ongoing TROPION-PanTumor03 phase 2 clinical trial have demonstrated encouraging efficacy of the combination of DATROWAY® (datopotamab deruxtecan) and rilvegostomig in patients with locally advanced or metastatic urothelial cancer. Presented today as a mini oral session (3072MO) at the 2025 European Society for Medical Oncology (#ESMO25) Congress, these findings suggest that this combination therapy could offer meaningful clinical benefit in both first-line and second-line treatment settings.
DATROWAY is a next-generation TROP2-directed DXd antibody-drug conjugate (ADC) developed by Daiichi Sankyo (TSE: 4568) and co-commercialized with AstraZeneca (LSE/STO/Nasdaq: AZN). Designed to selectively target TROP2-expressing tumor cells, DATROWAY delivers a cytotoxic payload to malignant cells, minimizing off-target effects. Rilvegostomig, on the other hand, is AstraZeneca’s innovative PD-1/TIGIT bispecific antibody, intended to enhance immune response against cancer cells by dual checkpoint blockade. The combination of these agents aims to harness both targeted cytotoxicity and immune-mediated tumor control, offering a potentially robust therapeutic option for patients with advanced urothelial cancer.
In this sub-study focusing on urothelial cancer, patients were treated in either the first-line or second-line setting. First-line patients were those ineligible for cisplatin therapy (n=22), while second-line patients had previously received platinum-based chemotherapy without prior immunotherapy exposure (n=18). The results showed that DATROWAY plus rilvegostomig achieved a confirmed objective response rate (ORR) of 68.2% (95% confidence interval [CI]: 45.1–86.1) and a disease control rate (DCR) of 95.5% (80% CI: 83.4–99.5) in the first-line cohort. Notably, median progression-free survival (PFS) was not reached in this group, and the PFS rate at 12 months was 73.5% (95% CI: 46.5–88.4), highlighting durable disease control for a significant proportion of patients.
In the second-line cohort, patients who had previously received platinum-based chemotherapy demonstrated a confirmed ORR of 38.9% (95% CI: 17.3–64.3) and a DCR of 83.3% (80% CI: 66.6–93.7). Median PFS was 12.5 months (95% CI: 4.2–NR), and the 12-month PFS rate was 60.0% (95% CI: 33.7–78.7). Importantly, median duration of response (DoR) had not yet been reached in either treatment setting, indicating that the responses observed were both robust and potentially long-lasting.
“This is a patient population with very limited treatment options,” said Dr. Sun Young Rha, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. “Despite advances in the management of metastatic urothelial cancer, many patients still experience progression after first-line therapy. The response rates observed with DATROWAY plus rilvegostomig, particularly the 95.5% disease control rate in the first-line setting, underscore the potential of this combination and support further evaluation across multiple lines of therapy.”
The safety profile of the combination therapy was consistent with known adverse events for both agents. In the first-line cohort, four of 22 patients (18.2%) experienced grade 3 or higher treatment-related adverse events (TRAEs), while seven of 18 patients (38.9%) in the second-line cohort experienced similar events. The most frequently reported grade 3 or higher TRAEs included increased amylase (13.6% first-line, 16.7% second-line), neutropenia (4.5%, 5.6%), stomatitis (0%, 5.6%), decreased appetite (0%, 5.6%), and anemia (0%, 5.6%). There was one case of interstitial lung disease (ILD) adjudicated as drug-related in the first-line setting (4.5%) and two cases in the second-line cohort (11.1%), though no grade 3 or higher ILD events were observed. Overall, these data suggest that the combination is generally tolerable, with manageable safety concerns.
The promising outcomes observed in TROPION-PanTumor03 have prompted further clinical development of DATROWAY in urothelial cancer. Daiichi Sankyo has launched the TROPION-Urothelial03 phase 2/3 trial, which evaluates DATROWAY in combination with platinum-based chemotherapy compared to standard-of-care gemcitabine plus platinum chemotherapy. This pivotal study targets patients with metastatic urothelial carcinoma who have progressed during or after treatment with enfortumab vedotin and pembrolizumab.
“The five-year survival rate for patients with metastatic urothelial cancer remains very low, emphasizing the urgent need for effective new therapies in this challenging disease setting,” said Dr. Abderrahmane Laadem, Head of Late-Stage Oncology Development at Daiichi Sankyo. “The results from TROPION-PanTumor03, together with earlier findings from TROPION-PanTumor01, reinforce our commitment to advancing DATROWAY as a treatment option for patients with urothelial cancer. With the initiation of TROPION-Urothelial03, we are undertaking our first pivotal trial outside breast and lung cancer, which represents a critical milestone in the clinical development of this agent.”
Leora Horn, Senior Vice President, Late Development Oncology at AstraZeneca, added, “These initial results support our strategy of combining the potent targeted activity of DATROWAY with dual PD-1/TIGIT checkpoint inhibition via rilvegostomig. By enhancing patients’ immune responses while delivering a cytotoxic payload directly to tumor cells, this combination has the potential to improve outcomes in patients with metastatic urothelial cancer. We are encouraged by the observed response rates and are eager to further explore this combination in the early-line setting.”
TROPION-PanTumor03 comprises seven sub-studies designed to evaluate DATROWAY both as a monotherapy and in combination with other approved or investigational therapies. The urothelial cancer sub-study (sub-study 6, cohort 6B) enrolled 40 patients, divided into first-line and second-line treatment groups. First-line patients included those ineligible for cisplatin with no prior systemic therapy or those who experienced disease progression more than 12 months after neoadjuvant or adjuvant therapy. Second-line patients had received prior platinum-based chemotherapy in either the metastatic or adjuvant/neoadjuvant setting, with progression occurring less than 12 months following therapy. Among the second-line cohort, six patients had prior adjuvant or neoadjuvant therapy, and twelve had prior treatment in the metastatic setting. Median follow-up duration was 10.8 months for first-line patients and 9.7 months for second-line patients, providing sufficient time to evaluate preliminary efficacy and safety outcomes.
Overall, the combination of DATROWAY and rilvegostomig demonstrated encouraging efficacy across both treatment lines, with particularly high disease control rates in the first-line setting. The tolerability profile was consistent with expectations, and no new safety signals were observed. These data provide strong support for the continued clinical development of this combination as a potential therapeutic option for patients with advanced urothelial cancer, a disease with significant unmet medical needs.
The promising results from TROPION-PanTumor03 highlight the potential of leveraging antibody-drug conjugates in combination with novel immunotherapy agents to achieve meaningful clinical outcomes. If future trials confirm these findings, DATROWAY plus rilvegostomig could emerge as an important new treatment paradigm for metastatic urothelial cancer, offering patients improved response rates and prolonged disease control while maintaining a manageable safety profile.
