Treating Urothelial Carcinoma with a Combination of Disitamab Vedotin plus Toripalimab
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on January 21st, 2026
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As a means to escape the immune system, many tumor cells express PD-1 on the surface to downregulate the immune cells that have specifically targeted them for killing. Interfere with this immune evasion method by targeting and inhibiting PD-1 had proven to be successful. The pharmaceutical RemeGen had funded a study to evaluate the added benefit of adding toripalimab - an anti-PD-1 immunotherapy - to the current therapy for urothelial carcinoma, disitamab vedotin.
The phase 3 clinical study was performed in China, and it included 484 participants with a median age of around 66 years old who had been diagnosed with unresectable, locally advanced or metastatic urothelial carcinoma. Around 94% of these patients were at stage IV disease, with the remaining in stage III. Biopsy of the tumor found that 22% of the patients had weak HER2 expression, 78% had moderate to high expression. PD-1 expression was also assessed and showed that half of the cohort had low expression and half had high expression.
The patients were randomly treated with either the combination of disitamab vedotin plus toripalimab or the standard chemotherapy containing gemcitabine plus cisplatin or carboplatin. Disitamab vedotin is a conjugated structure that includes an antibody targeting HER2 linked to monomethyl auristatin E, which is an anti-mitotic agent that blocks cell division by interfering with tubulin assembly. This conjugate is administered intravenously at a dose of 2.0 mg per kilogram of body weight once every two weeks. At the same time, the anti-PD-1 toripalimab is also given at a dose of 3.0 mg per kilogram of body weight.
After a median follow-up time of 18.2 months, the researchers found that patients treated with the combination of disitamab vedotin & toripalimab had an average progression-free survival time of 13.1 months, which was significantly longer than the 6.5 months observed in the group treated with standard chemotherapy. Additionally, the cohort treated with disitamab vedotin & toripalimab has a significantly longer overall survival time of 31.5 months compared to the control group, which has a survival time of 16.9 months. The combo of disitamab vedotin & toripalimab is also effective targeting the tumor, as 76.1% of the group had complete or partial shrinkage of the tumor, which is only reported by 50.2% of the chemotherapy group. Beside its clinical benefit, the disitamab vedotin plus toripalimab regimen is more well-tolerated with less adverse effects than those treated with chemotherapy. Future studies should consider expanding the ethnic diversity of the treated patients, and perform comparison between disitamab vedotin treatment with and without toripalimab to fully understand the efficacy and necessity of each component in the therapy.
The phase 3 clinical study was performed in China, and it included 484 participants with a median age of around 66 years old who had been diagnosed with unresectable, locally advanced or metastatic urothelial carcinoma. Around 94% of these patients were at stage IV disease, with the remaining in stage III. Biopsy of the tumor found that 22% of the patients had weak HER2 expression, 78% had moderate to high expression. PD-1 expression was also assessed and showed that half of the cohort had low expression and half had high expression.
The patients were randomly treated with either the combination of disitamab vedotin plus toripalimab or the standard chemotherapy containing gemcitabine plus cisplatin or carboplatin. Disitamab vedotin is a conjugated structure that includes an antibody targeting HER2 linked to monomethyl auristatin E, which is an anti-mitotic agent that blocks cell division by interfering with tubulin assembly. This conjugate is administered intravenously at a dose of 2.0 mg per kilogram of body weight once every two weeks. At the same time, the anti-PD-1 toripalimab is also given at a dose of 3.0 mg per kilogram of body weight.
After a median follow-up time of 18.2 months, the researchers found that patients treated with the combination of disitamab vedotin & toripalimab had an average progression-free survival time of 13.1 months, which was significantly longer than the 6.5 months observed in the group treated with standard chemotherapy. Additionally, the cohort treated with disitamab vedotin & toripalimab has a significantly longer overall survival time of 31.5 months compared to the control group, which has a survival time of 16.9 months. The combo of disitamab vedotin & toripalimab is also effective targeting the tumor, as 76.1% of the group had complete or partial shrinkage of the tumor, which is only reported by 50.2% of the chemotherapy group. Beside its clinical benefit, the disitamab vedotin plus toripalimab regimen is more well-tolerated with less adverse effects than those treated with chemotherapy. Future studies should consider expanding the ethnic diversity of the treated patients, and perform comparison between disitamab vedotin treatment with and without toripalimab to fully understand the efficacy and necessity of each component in the therapy.