Disitamab vedotin plus toripalimab extends PFS, OS in HER2-positive la/mUC

The phase 3 RC48-C016 trial (NCT05302284), evaluating first-line disitamab vedotin (DV; RC 48) plus toripalimab in patients with HER2-expressing locally advanced or metastatic urethelial carcinoma (la/mUC), has reached its dual primary end points of progression-free survival (PFS) and overall survival (OS), RemeGen Co announced in a news release.¹

The combination also demonstrated a manageable safety profile.

A prespecified interim analysis by the Independent Data Monitoring Committee found that the combination significantly improved PFS and OS vs standard chemotherapy in this patient population. These benefits were seen regardless of cisplatin eligibility or HER2 expression level.

According to the company, the safety profile for the combination was manageable, with tolerable adverse events.

"We, once again, jointly witnessed a strong positive result of DV combined with toripalimab in the first-line treatment of advanced urothelial carcinoma,” said principal investigator, professor Guo Jun of Peking University Cancer Hospital, in the news release.¹ “Regardless of whether the patients are suitable for cisplatin treatment and regardless of patients' HER2 expression status, DV combined with toripalimab significantly improved PFS and OS. This outstanding efficacy proves the success of the 'HER2-ADC + immunotherapy' combination treatment concept and is also a major breakthrough in the global treatment of urothelial carcinoma. We look forward to the excellent performance of DV in subsequent studies, which should provide better decision-making basis for clinicians, bring more benefits to patients, and reshape the global treatment landscape of urothelial carcinoma with the 'Chinese approach'."

Based on these results, RemeGen plans to file a biologic license application to China’s Center of Drug Evaluation of National Medical Products Administration for this indication. The company also plans to share detailed results from the study at upcoming medical meetings.

In September 2020, the FDA granted a breakthrough therapy designation for DV, an antibody-drug conjugate, for the second-line treatment of patients with HER2-positive la/mUC who had previously received platinum-containing chemotherapy.²

About the RC48-C016 trial

In total, the phase 3, open-label trial enrolled 484 patients with treatment-naïve HER2-positive la/mUC across 74 clinical trials sites in China. Participants in the study were randomly assigned to receive DV plus toripalimab every 2 weeks or to gemcitabine in combination with cisplatin/carboplatin every 3 weeks for a maximum of 6 weeks or until loss of clinical benefit, unacceptable toxicity, withdrawal from study, or death.

To be eligible for enrollment, patients needed to have an expected survival of at least 12 weeks, at least 1 measurable lesion per RECIST v1.1, and ECOG performance state of 0 or 1, HER2-expressing status (IHC 1+, 2+, or 3+), and adequate cardiac, bone marrow, hepatic, renal, and coagulation functions. Additionally, patients could not have received prior systemic therapy for la/mUC.³

The dual primary end points for the study are PFS and OS. The study is also evaluating objective remission rate, duration of relief, and disease control rate.

Primary completion of the study is planned for December 2026.

REFERENCES

1. Poised to reshape treatment landscape: The phase 3 clinical trial of 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 Co, Ltd. Published online and accessed May 12, 2025. https://www.prnewswire.com/news-releases/poised-to-reshape-treatment-landscape-the-phase-3-clinical-trial-of-disitamab-vedotin-as-a-first-line-therapy-for-her2-expressing-locally-advanced-or-metastatic-urothelial-carcinoma-reached-its-primary-endpoints-of-pfs-and-os-302452193.html

2. RemeGen announces US FDA has granted Breakthrough Therapy Designation for disitamab vedotin (RC48) in urothelial cancer. News release. September 25, 2020. Accessed May 12, 2025. https://www.prnewswire.com/news-releases/remegen-announces-us-fda-has-granted-breakthrough-therapy-designation-for-disitamab-vedotin-rc48-in-urothelial-cancer-301138315.html

3. A study of RC48-ADC combined with toripalimab for first-line treatment of urothelial carcinoma. ClinicalTrials.gov. Last updated December 18, 2023. Accessed May 12, 2025. https://clinicaltrials.gov/study/NCT05302284