Subcutaneous Toripalimab Plus Disitamab Vedotin sNDA Is Accepted in China for HER2-Expressing Urothelial Cancer

China's National Medical Products Administration (NMPA) has accepted a supplemental new drug application seeking the approval of a subcutaneous formulation of toripalimab (Loqtorzi; JS001sc) in combination with disitamab vedotin (Aidixi) as first-line treatment for patients with HER2-expressing locally advanced or metastatic urothelial carcinoma.¹ The application covers tumors with a HER2 immunohistochemistry score of 1+, 2+, or 3+.

With this filing, the NMPA has now accepted applications for subcutaneous toripalimab across all 13 indications for which intravenous toripalimab is approved in China. The agency accepted applications for 12 of those indications in March 2026, making JS001sc the first domestically developed subcutaneous anti–PD-1 monoclonal antibody in China to reach the new drug application stage.

In May 2026, the NMPA approved intravenous toripalimab plus disitamab vedotin for first-line treatment of HER2-expressing locally advanced or metastatic urothelial carcinoma, marking the 13th approved indication for toripalimab in mainland China.² Toripalimab had previously been approved in China in 2021 for advanced urothelial carcinoma in the second line or later.

The regulatory decision for the frontline combination was based on findings from the phase 3 RC48-C016 trial (NCT05302284), which enrolled patients at 74 centers across China.

RC48-C016 was a multicenter, open-label, randomized phase 3 trial in which 484 patients with previously untreated HER2-expressing locally advanced or metastatic urothelial cancer were randomly assigned 1:1 to disitamab vedotin plus toripalimab every 2 weeks or gemcitabine plus cisplatin or carboplatin every 3 weeks.³

Progression-free survival (PFS) by blinded independent review and overall survival (OS) served as dual primary end points, and secondary end points included objective response and safety.

At a median follow-up of 18.2 months, the median PFS was 13.1 months with the combination vs 6.5 months with chemotherapy (HR, 0.36; 95% CI, 0.28-0.46; P < .001). Additionally, the respective median OS values were 31.5 vs 16.9 months (HR, 0.54; 95% CI, 0.41-0.73; P < .001). The objective response rate (ORR) was 76.1% (95% CI, 70.3%-81.3%) vs 50.2% (95% CI, 43.7%-56.7%).

Median duration of response was 14.6 months with the combination vs 5.6 months with chemotherapy.²

Grade 3 or higher treatment-related adverse effects (AEs) occurred in 55.1% of patients in the combination arm and 86.9% of those in the chemotherapy arm.³

What are the mechanisms of action of toripalimab and disitamab vedotin?

Toripalimab is an anti–PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, and also induces internalization of the PD-1 receptor. Disrupting this signaling helps restore the immune system’s ability to recognize and attack tumor cells.²

Disitamab vedotin is a HER2-directed antibody-drug conjugate composed of a humanized antibody, a protease-cleavable linker, and the cytotoxic payload monomethyl auristatin E. After binding to HER2 and being internalized by tumor cells, the conjugate releases its microtubule-disrupting payload. The combination therefore pairs targeted cytotoxic delivery with immune checkpoint inhibition.

What data support the subcutaneous formulation?

Evidence for subcutaneous toripalimab has been derived from the phase 3 JS001sc-002-III-NSCLC study (NCT06505837), which compared subcutaneous with intravenous toripalimab, each given with chemotherapy, in patients with recurrent or metastatic nonsquamous non–small cell lung cancer (NSCLC).¹ The study met its primary end point in November 2025. In an oral presentation at the 2026 European Lung Cancer Congress, investigators reported that toripalimab exposure with the subcutaneous formulation was noninferior to that of the intravenous version, with similar efficacy and safety.

How was the JS001sc-002-III-NSCLC study designed?

JS001sc-002-III-NSCLC is an open-label, randomized, multicenter phase 3 trial comparing the pharmacokinetics, efficacy, and safety of subcutaneous and intravenous toripalimab, each combined with chemotherapy, as first-line therapy for recurrent or metastatic nonsquamous NSCLC.⁴

Patients were randomly assigned 1:1 to subcutaneous toripalimab 360 mg or intravenous toripalimab 240 mg, each given every 3 weeks, along with pemetrexed and cisplatin or carboplatin for 4 cycles. Those whose disease had not progressed then received maintenance pemetrexed with their assigned toripalimab formulation, with total toripalimab treatment capped at 35 cycles.

The study’s primary end points were the observed serum trough concentration at the end of cycle 1 and the model-predicted area under the concentration-time curve from day 0 to day 21 of cycle 1. Secondary end points included ORR, PFS, 6-month PFS rate, disease control rate, duration of response, and safety, which was assessed through AEs and abnormal laboratory parameters.

References

1. Junshi Biosciences announces acceptance of the supplemental new drug application of toripalimab (subsutaneous injection) for the 1st-line treatment of HER2-expressing urothelial carcinoma. News release. Junshi Biosciences. October 28, 2026. Accessed October 29, 2026. https://www.globenewswire.com/news-release/2026/10/29/3390884/0/en/junshi-biosciences-announces-acceptance-of-the-supplemental-new-drug-application-of-toripalimab-subsutaneous-injection-for-the-1st-line-treatment-of-her2-expressing-urothelial-carc.html
2. Junshi Biosciences announces approval of toripalimab NDA for the 1st-line treatment of HER2 expressing urothelial carcinoma. News release. Junshi Biosciences. May 21, 2026. Accessed October 29, 2026. https://www.globenewswire.com/news-release/2026/05/21/3299131/0/en/Junshi-Biosciences-Announces-Approval-of-Toripalimab-NDA-for-the-1st-line-treatment-of-HER2-Expressing-Urothelial-Carcinoma.html
3. Sheng X, Zeng G, Zhang C, et al. Disitamab vedotin plus toripalimab in HER2-expressing advanced urothelial cancer. N Engl J Med. 2025;393(23):2324-2337. doi:10.1056/NEJMoa2511648
4. JS001sc or JS001 plus chemotherapy is indicated for relapsed or metastatic first-line non-squamous non small cell lung cancer (NSCLC). ClinicalTrials.gov. Updated August 28, 2025. Accessed October 29, 2026. https://clinicaltrials.gov/study/NCT06505837