Junshi, Remegen pick up China nod for toripalimab plus disitamab vedotin in HER2+ urothelial carcinoma

Edited by Robert McTiernan··4 min read

Shanghai Junshi Biosciences (HKEX: 1877; SSE: 688180) has received approval from China’s National Medical Products Administration (NMPA) for Tuoyi (toripalimab) in combination with disitamab vedotin as a first-line treatment for HER2-expressing locally advanced or metastatic urothelial carcinoma (UC). This week’s new approval nod marks the 13th approved indication for toripalimab in mainland China and the first approval in the country specifically targeting HER2-expressing UC in the first-line setting.

The approval covers patients with HER2-positive tumors who are systemic-treatment-naive, a broad biomarker definition that encompasses a substantial proportion of the UC patient population. Disitamab vedotin, an antibody-drug conjugate (ADC) independently developed by RemeGen Co., Ltd, is directed against HER2 and delivers a cytotoxic payload selectively to HER2-expressing tumor cells. Toripalimab, an anti-PD-1 monoclonal antibody, blocks PD-1 interactions with PD-L1 and PD-L2 and induces PD-1 receptor internalization, augmenting T-cell-mediated anti-tumor activity. The combination pairs targeted cytotoxicity with immune checkpoint inhibition in a biomarker-selected population.

Clinical evidence from the RC48-C016 study

The approval is supported by data from the RC48-C016 study (NCT05302284), a Phase III, multi-center, randomized, open-label, controlled trial conducted across 74 clinical centers in China. The trial enrolled systemic-treatment-naive patients with HER2-expressing locally advanced or metastatic UC and compared toripalimab plus disitamab vedotin against gemcitabine combined with cisplatin or carboplatin. The co-primary endpoints were progression-free survival assessed by blinded independent review and overall survival.

Results published in the New England Journal of Medicine in October 2025 and presented at the ESMO 2025 Presidential Symposium showed the combination more than doubled median PFS compared with chemotherapy — 13.1 months versus 6.5 months (hazard ratio 0.36, 95% CI 0.28–0.46; p < 0.0001). Median OS was 31.5 months in the combination arm versus 16.9 months with chemotherapy (HR 0.54, 95% CI 0.41–0.73; p < 0.0001). The objective response rate was 76.1% versus 50.2%, and median duration of response was 14.6 months versus 5.6 months.

Mechanistic rationale and competitive context

The pairing of a HER2-directed ADC with a PD-1 inhibitor reflects a broader strategy of combining targeted tumor killing with immune activation. Disitamab vedotin delivers its cytotoxic payload to HER2-expressing cells, and the resulting immunogenic cell death may enhance the anti-tumor immune response that toripalimab sustains by relieving PD-1-mediated T-cell suppression. The broad HER2 biomarker definition — extending to IHC 1+ — expands the eligible population beyond the HER2-high subset typically targeted in breast or gastric cancer settings, which is clinically relevant given the distribution of HER2 expression across UC tumors.

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In the global first-line urothelial cancer therapy landscape, the most structurally comparable approved regimen is enfortumab vedotin plus pembrolizumab, which received full US FDA approval in December 2023 based on the EV-302 trial. That combination — a Nectin-4-directed ADC paired with an anti-PD-1 inhibitor — is biomarker-agnostic and has established itself as a benchmark for first-line locally advanced or metastatic UC. The toripalimab plus disitamab vedotin regimen differs in its HER2-directed mechanism and biomarker-selected population, and the RC48-C016 data were generated in a Chinese patient cohort without direct cross-trial comparison to EV-302.

The NMPA approval positions the combination as a first-line option specifically for the HER2-expressing UC population in China, where the incidence of UC has been rising. The company reported 92,900 new UC cases in China in 2022, with more than 40,000 deaths, citing data from the National Cancer Center. Toripalimab had previously received NMPA approval in 2021 for second-line and above treatment of advanced UC in a non-biomarker-selected population, making this new indication an expansion into the first-line HER2-selected setting.

With 13 approved indications in mainland China, toripalimab now spans a broad range of tumor types including lung, nasopharyngeal, esophageal, bladder, breast, liver, renal, and skin cancers. The first 12 indications have been included in China’s National Reimbursement Drug List (2025 edition). Internationally, toripalimab has received marketing authorization in more than 40 countries and regions, including the US, EU, UK, Australia, and India.

The RC48-C016 data represent one of the more mature readouts for an ADC plus PD-1 inhibitor combination in UC, with both PFS and OS endpoints met and results published in a high-profile journal prior to regulatory approval. It remains to be seen whether the HER2-targeting approach will translate to regulatory submissions outside China.

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