disitamab vedotin

Overview

Disitamab vedotin (DV; RC48; Aidixi) is a HER2-directed antibody–drug conjugate developed for HER2-expressing solid tumors. It is approved for several indications in China but remains investigational in the United States; FDA orphan-drug designation does not constitute marketing approval. Clinical development includes urothelial, gastric/gastroesophageal-junction and breast cancers, including some tumors with low HER2 expression. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

DV consists of the humanized anti-HER2 antibody disitamab conjugated through a protease-cleavable linker to monomethyl auristatin E (MMAE). After HER2 binding and internalization, MMAE is released and inhibits microtubule polymerization, causing cell-cycle arrest and death. Membrane-permeable MMAE may also kill neighboring cells with lower HER2 expression—the proposed “bystander effect.” (pmc.ncbi.nlm.nih.gov)

Efficacy

• First-line urothelial cancer: In a randomized phase III trial involving 484 patients with HER2-expressing advanced urothelial cancer, DV plus toripalimab improved median progression-free survival versus platinum chemotherapy (13.1 vs 6.5 months; HR 0.36) and median overall survival (31.5 vs 16.9 months; HR 0.54). Objective response rates were 76.1% and 50.2%, respectively. (nejm.org)
• Previously treated urothelial cancer: A combined analysis of two single-arm phase II studies found an independently assessed response rate of 50.5% among 107 patients. Median response duration was 7.3 months, progression-free survival 5.9 months and overall survival 14.2 months. (ascopubs.org)
• HER2-positive breast cancer with liver metastases: A randomized phase III trial found longer progression-free survival with DV than with lapatinib plus capecitabine (9.9 vs 4.9 months; HR 0.56) after prior trastuzumab and taxane therapy. (nature.com)
• Advanced breast cancer, early-phase data: At 2 mg/kg every two weeks, response rates were 42.9% in HER2-overexpressing disease and 33.3% in HER2-low disease; median progression-free survival was 5.7 and 5.1 months, respectively. (pubmed.ncbi.nlm.nih.gov)
• Gastric/gastroesophageal-junction cancer: In a phase I combination study, DV plus toripalimab produced a confirmed response rate of 43% overall and 50% at the recommended phase II dose; median progression-free survival was 6.2 months. These findings remain less definitive than randomized phase III evidence. (pubmed.ncbi.nlm.nih.gov)

Safety

Peripheral sensory neuropathy, leukopenia/neutropenia, fatigue or asthenia and elevated liver enzymes are recurring toxicities. In the previously treated urothelial-cancer studies, 54.2% experienced grade 3 or higher treatment-related adverse events, most notably peripheral neuropathy (18.7%) and neutropenia (12.1%). (ascopubs.org)

In first-line urothelial cancer, grade 3 or higher treatment-related events occurred in 55.1% with DV plus toripalimab versus 86.9% with chemotherapy. In the breast-cancer phase III trial, corresponding rates were 37.7% with DV and 36.0% with lapatinib–capecitabine. Rare serious events reported in combination studies include pneumonitis, including a treatment-related death. (nejm.org)

Further reading

• Phase III trial in first-line urothelial cancer
• Phase II urothelial-cancer analysis
• Phase III breast-cancer trial
• Phase I/Ib breast-cancer study
• DV plus toripalimab in gastric and other solid tumors

Last updated: Sep 2026