Disitamab vedotin and Cadonilimab combination therapy

The combination of *disitamab vedotin* (DV, RC48-ADC) and *cadonilimab* represents a novel therapeutic approach being investigated for various cancers, particularly those expressing HER2. This combination pairs an antibody-drug conjugate targeting HER2 with a bispecific antibody targeting PD-1/CTLA-4 immune checkpoints. *Disitamab vedotin* is a humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE), designed to selectively kill HER2-expressing tumor cells[1][10]. *Cadonilimab* (AK104) is a tetravalent bispecific antibody targeting both PD-1 and CTLA-4 immune checkpoints, with an Fc-null design that eliminates antibody-dependent cellular cytotoxicity and other Fc-mediated effects, potentially reducing toxicity compared to combination therapy with separate PD-1 and CTLA-4 inhibitors[6][9]. The combination is being investigated in several clinical trials for different cancer types. For locally advanced or metastatic urothelial carcinoma (la/mUC), preliminary results from a study showed promising efficacy with an objective response rate (ORR) of 75.0% and disease control rate (DCR) of 100%[1]. The combination is also being studied in muscle-invasive bladder cancer (MIBC) as neoadjuvant and adjuvant therapy[2], and in HER2-expressing gastric cancer and gastroesophageal junction adenocarcinoma after progression on first-line therapy[5]. The theoretical basis for this combination is that *disitamab vedotin* not only kills HER2-expressing tumor cells selectively but also enhances the immune response triggered by *cadonilimab*, potentially creating synergistic anti-tumor effects[3][8]. This approach may be particularly valuable for patients who cannot tolerate standard treatments like cisplatin-based chemotherapy[1][2]. Common treatment-related adverse events include increased AST/ALT, fever, anemia, rash, and pruritus. More serious adverse events include immune-related reactions affecting the skin, liver, and colon[1]. Infusion-related reactions have been documented with *cadonilimab*, which can be managed with pretreatment medications and adjusting infusion rates[6]. This combination therapy represents an innovative approach in cancer treatment, combining targeted therapy with immunotherapy to potentially improve outcomes for patients with HER2-expressing tumors who have limited treatment options.