Disitamab Vedotin plus Toripalimab significantly improved progression-free and overall survival compared to chemotherapy in untreated HER2-expressing advanced urothelial cancer. The combination therapy had a more favorable safety profile, particularly regarding hematologic toxic effects. Objective response rates were also notably higher with the combination therapy.
Study
|
Phase 3, multicenter, open-label, randomized trial [RC48-C016] |
| Untreated HER2-expressing (IHC score 1+, 2+, or 3+) locally advanced or metastatic urothelial cancer |
| Disitamab Vedotin plus Toripalimab (n=243) vs chemotherapy (gemcitabine plus cisplatin or carboplatin, n=241)
|
Efficacy
|
ORR: 76.1% [70.3-81.3] vs 50.2% [43.7-56.7] |
| mPFS: 13.1 mos vs 6.5 mos (HR 0.36 [0.28-0.46]) |
| mOS: 31.5 mos vs 16.9 mos (HR 0.54 [0.41-0.73])
|
Safety
|
Grade >=3 AE: Neutropenia (5.8% vs 61.7%), anemia (5.3% vs 45.5%). |
| Peripheral neuropathy (4.1% vs 0%), hypoesthesia (5.3% vs 0%). |
| Treatment discontinuations due to AE: 12.3% vs 10.4%.
|
N Engl J Med. Published online October 19, 2025
http://doi.org/10.1056/NEJMoa2511648
Reviewed by Ulas D. Bayraktar, MD on Nov 13, 2025
