TROP2 ADC demonstrates promising antitumor activity in urothelial carcinoma

The TROP2 antibody-drug conjugate sacituzumab tirumotecan (sac-TMT) demonstrated encouraging preliminary antitumor activity with a manageable safety profile in patients with advanced or metastatic urothelial carcinoma (UC) whose tumors progressed on chemotherapy and immune checkpoint inhibitors, according to data from cohort 9 of the phase 2 MK-2870-001/KL264-01 trial (NCT04152499).¹

"Traditional chemotherapy has limited efficacy for advanced or drug-resistant UC,” explained Dingwei Ye, MD, PhD, vice president of Fudan University Shanghai Cancer Center, in a news release on the study results.² “The emergence of precision medicines like ADCs is breaking through treatment bottlenecks for patients with poor response to chemotherapy.”

In total, the study included 49 patients with UC who received treatment with 5 mg/kg of sac-TMT monotherapy intravenously every 2 weeks. Among all patients, 76% had received at least 2 lines of prior therapy. The median age of participants was 61 years (range 40 to 76 years).

The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

At a median follow-up of 18.8 months (range, 15.1 to 25), the confirmed ORR was 31% (95% CI, 18 to 45), and the disease control rate (defined as complete response plus partial response plus stable disease) was 71% (95% CI, 57 to 83). This included a complete response rate of 2% and a partial response rate of 29%; 41% of patients had stable disease.

Among those who received sac-TMT as a second-line therapy (n = 12), the confirmed ORR was 50% (95% CI, 21 to 79) and the DCR was 75% (95% CI, 43 to 95). For those who received sac-TMT as a third-line therapy or later (n = 37), the confirmed ORR was 24% (95% CI, 12 to 41) and the DCR was 70% (95% CI, 53 to 84).

At the time of data report, the median DOR for the entire cohort had not been reached (range, 2.1 to 22.2+ months). The 12-month probability of sustained response was 53%.

Further, the median PFS was 5.5 months (95% CI, 3.6 to 7.2), and the median OS was 12.1 months (95% CI, 9.9 to 15.3) among all patients in the trial. The 18-month rates of PFS and OS were 26% and 33%, respectively.

In patients who received sac-TMT as a second-line therapy, the median PFS was 5.8 months (95% CI, 1.7 to NE), and the median OS was not reached (95% CI, 2.0 to NE). The median PFS was 4.3 months (95% CI, 3.5 to 7.2) and the median OS was 11.5 months (95% CI, 8.9 to 13.9) among those who received sac-TMT in the third-line setting or later.

Regarding safety, grade 3 to 4 treatment-related adverse events (TRAEs) were reported in 63% of patients (n = 31) across the entire cohort. The most common TRAEs were anemia (41%), decreased neutrophil count (35%), decreased white blood cell count (20%), stomatitis (12%), and decreased platelet count (8%). No grade 5 TRAEs nor febrile neutropenia were observed.

Based on these results, Dingwei concluded, “We are delighted to observe the encouraging clinical outcomes achieved by the sac-TMT monotherapy regimen, particularly its outstanding efficacy even among heavily pretreated patients. This development injects new momentum into the treatment landscape for advanced UC and offers patients a more precise therapeutic option."

REFERENCES

1. Zhu Y, Jiang S, Shi Y, et al. Sacituzumab tirumotecan in participants with advanced or metastatic urothelial carcinoma and disease progression after chemotherapy and immune checkpoint inhibitors. Ann Oncol. 2025:S0923-7534(25)06272-6. doi:10.1016/j.annonc.2025.11.013

2. The Annals of Oncology publishes results of phase II study of sacituzumab tirumotecan monotherapy for urothelial carcinoma. News release. Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. November 28, 2025. Accessed December 2, 2025. https://www.prnewswire.com/news-releases/the-annals-of-oncology-publishes-results-of-phase-ii-study-of-sacituzumab-tirumotecan-monotherapy-for-urothelial-carcinoma-302627874.html