NMPA Accepts sNDA for Frontline Toripalimab Plus Disitamab Vedotin in HER2+ Urothelial Carcinoma

China’s National Medical Products Administration (NMPA) has accepted the supplemental new drug application (sNDA) seeking the approval of toripalimab (Loqtorzi) in combination with the novel antibody-drug conjugate disitamab vedotin (PF-08046051) for the first-line treatment of patients with HER2-expressing locally advanced or metastatic urothelial carcinoma.1

The sNDA is supported by data from the phase 3 RC48-C016 study (NCT05302284). In May 2025, RemGen announced that toripalimab plus disitamab vedotin met the dual primary end points of RC48-C016.2 Findings from the prespecified interim analysis of the trial demonstrated that patients with treatment-naïve, HER2-expressing locally advanced or metastatic urothelial carcinoma who received the combination achieved significant and clinically meaningful benefits in terms of progression-free survival (PFS) and overall survival (OS) compared with those treated with chemotherapy.

Additionally, data from the primary subgroup analysis revealed that toripalimab plus disitamab vedotin significantly improved PFS and OS vs chemotherapy regardless of cisplatin eligibility or HER2 expression level. In terms of safety, the combination displayed a manageable safety profile and tolerable adverse effects.

Detailed findings from are planned to be presented at major international academic conferences later in 2025.

RC48-C016 was anopen-label, randomized, multicenter that enrolled 484 adult patients with systemic-treatment-naive, HER2-expressing (immunohistochemistry 1+, 2+, or 3+) locally advanced or metastatic urothelial carcinoma across 74 sites in China.2,3 Patients were required to have a life expectancy of at least 12 weeks, at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, as well as adequate cardiac, bone marrow, hepatic, renal, and coagulation function.

Prior neoadjuvant chemotherapy followed by disease recurrence more than 6 months after the completion of therapy was allowed. Additionally, patients who received adjuvant chemotherapy following cystectomy who experienced disease recurrence over 6 months after the completion of therapy were permitted to enroll.

In the experimental arm, patients received intravenous (IV) toripalimab at 3.0 mg/kg every 2 weeks in combination with IV disitamab vedotin at 2.0 mg/kg every 2 weeks. Patients in the active comparator arm received IV gemcitabine at 1000 mg/m2 on days 1 and 8 of every 3-week cycle in combination with IV cisplatin at 70 mg/m2 on day 1 of each cycle or IV carboplatin at an area under the concentration curve of 4.5 on day 1 of each cycle, all for up to 6 weeks. Treatment in both arms continued until loss of clinical benefit, unacceptable toxicity, patient withdrawal, or death.

The coprimary end points were PFS by independent review committee per RECIST 1.1 criteria and OS. Secondary end points included overall response rate, duration of response, and disease control rate.

Toripalimab holds 12 approved indications in the Chinese mainland and was the first domestic anti–PD-1 monoclonal antibody approved for marketing in the country.1 The agent has also received approval in the United States, 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.globenewswire.com/news-release/2025/08/08/3130114/0/en/Junshi-Biosciences-Announces-the-Acceptance-of-the-sNDA-for-Toripalimab-as-the-1st-line-Treatment-of-HER2-expressing-Urothelial-Carcinoma.html
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. Updated December 18, 2023. Accessed August 8, 2025. https://clinicaltrials.gov/study/NCT05302284