First-line disitamab vedotin plus toripalimab under review in China for la/mUC

China’s National Medical Products Administration (NMPA) has accepted a supplemental new drug application (sNDA) seeking approval of disitamab vedotin (PF-08046051) in combination with toripalimab (Loqtorzi, US; Tuoyi, China) for the first-line treatment of patients with HER2-expressing locally advanced or metastatic urothelial carcinoma (la/mUC), Junshi Biosciences announced in a news release.¹

The sNDA is supported by data from the phase 3 RC48-C016 study (NCT05302284), which met its primary end points by demonstrating that toripalimab plus disitamab vedotin significantly improved progression-free survival (PFS) and overall survival (OS) vs gemcitabine plus cisplatin/carboplatin in patients with HER2-expressing la/mUC. These efficacy benefits were observed irrespective of cisplatin eligibility or HER2 expression level.

The safety profile for toripalimab was also consistent with previous studies, and no new safety signals were identified.

Data from the trial are expected to be presented at upcoming international medical meetings.

“The strongly positive results of [disitamab vedotin] in combination with toripalimab as a first-line treatment for advanced urothelial carcinoma are encouraging,” said Jun Guo, MD, PhD, principal investigator of the study and professor at Peking University Cancer Hospital, in a prior news release on the findings.² “[Disitamab vedotin] combined with toripalimab significantly improved PFS and OS, irrespective of cisplatin eligibility or HER2 expression level, which proves the success of HER2-ADC plus immunotherapy and represents a major breakthrough in the treatment of urothelial carcinoma worldwide. It is expected that the excellent performance of disitamab vedotin in subsequent studies will provide better decision-making basis for clinicians, bring more benefits to patients, and reshape the global treatment landscape of urothelial carcinoma with the Chinese regimen.”

In total, the open-label RC48-C016 trial enrolled 484 patients across 74 clinical trial sites in China.² Patients enrolled in the study had not received prior systemic therapy and had tumors that expressed HER2 (defined as a HER2 immunohistochemistry test result of 1+, 2+, or 3+).

Those enrolled in the study were randomly assigned to receive 3.0 mg/kg IV toripalimab plus 2.0 mg/kg IV disitamab vedotin every 2 weeks or to gemcitabine plus cisplatin or carboplatin every 3 weeks.³ The trial’s primary end points were PFS and OS. Secondary end points include objective remission rate, duration of relief, and disease control rate, all assessed for up to 3 years.

Final completion of the study is expected in April 2028.

Toripalimab is currently approved under 12 indications in China. In 2021, the anti-PD-1 monoclonal antibody received NMPA approval for the second-line and above treatment of advanced UC. This approval marked the “first immunotherapy drug approved for non-selective, population-based indications of advanced UC in China.”¹

Toripalimab has also received approvals in the US, the European Union, India, the United Kingdom, Jordan, Australia, Singapore, United Arab Emirates, Kuwait and other countries.

REFERENCES

1. Junshi Biosciences announces the acceptance of the sNDA for toripalimab as the 1st-line treatment of HER2-expressing Urothelial Carcinoma. News release. Junshi Biosciences. August 8, 2025. Accessed August 8, 2025. https://www.junshipharma.com/en/junshi-biosciences-announces-the-snda-approval-of-toripalimab-for-the-1st-line-treatment-of-melanoma/

2. Poised to reshape treatment landscape: A phase 3 clinical trial on disitamab vedotin as a first-line therapy for HER2-expressing locally advanced or metastatic urothelial carcinoma reached its primary endpoints of PFS and OS. News release. RemeGen. May 12, 2025. Accessed August 8, 2025. https://www.remegen.com/index.php?v=show&cid=115&id=2596

3. A study of RC48-ADC combined with toripalimab for first-line treatment of urothelial carcinoma. ClinicalTrials.gov. Last updated December 18, 2023. Accessed August 8, 2025. https://clinicaltrials.gov/study/NCT05302284