Disitamab Vedotin Combo Extends PFS/OS in HER2+ Urothelial Carcinoma

Investigators plan to share detailed results from the RC48-C016 trial at future international academic conferences in 2025.

Combining disitamab vedotin with toripalimab (Loqtorzi) as frontline therapy reached the primary end points of progression-free survival (PFS) and overall survival (OS) among patients with HER2-expressing locally advanced or metastatic urothelial carcinoma, according to a press release on findings from the phase 3 RC48-C016 trial (NCT05302284).¹

Based on a prespecified interim analysis from an independent data monitoring committee, the disitamab vedotin combination yielded statistically significant and clinically meaningful PFS and OS outcomes vs standard chemotherapy. Additionally, subgroup analyses showed that the experimental regimen extended survival in patients regardless of cisplatin eligibility or HER2 expression level.

Disitamab vedotin plus toripalimab produced a manageable safety profile and tolerable adverse effects in the trial.

Investigators plan to share detailed results from the RC48-C016 trial at future international academic conferences in 2025. Additionally, developers look to file a biologics license application for the disitamab vedotin combination to China’s Center for Drug Evaluation of the National Medical Products Administration.

“We, once again, jointly witnessed a strong positive result of [disitamab vedotin] combined with toripalimab in the first-line treatment of advanced urothelial carcinoma. Regardless of whether the patients are suitable for cisplatin treatment and regardless of patients’ HER2 expression status, [disitamab vedotin] combined with toripalimab significantly improved PFS and OS,” principal study investigator and professor Guo Jun, from Peking University Cancer Hospital, stated in the press release.¹ “This outstanding efficacy proves the success of the HER2 [antibody-drug conjugate plus] immunotherapy combination treatment concept and is also a major breakthrough in the global treatment of urothelial carcinoma.”

Investigators of the multicenter, active-controlled, randomized phase 3 RC48-C016 study are assessing the safety and efficacy of disitamab vedotin plus toripalimab vs gemcitabine plus cisplatin/cisplatin as frontline systemic therapy for patients with HER2-expressing locally advanced or metastatic urothelial carcinoma. The study began in June 2022, and investigators are evaluating 484 patients in 74 sites across China.

In the experimental arm, patients received disitamab vedotin at 2.0 mg/kg intravenously every 2 weeks in combination with toripalimab at 3.0 mg/kg intravenously every 2 weeks.² Patients in the comparator arm received gemcitabine at 1000 mg/m² intravenously on days 1 and 8 of every 3-week cycle, cisplatin at 70 mg/m² intravenously on day 1, and carboplatin at area under the curve 4.5 intravenously on day 1.

The trial’s primary end points were PFS per independent review committee assessment using RECIST v1.1 criteria and OS. Secondary end points included objective response rate, investigator-assessed PFS, duration of response, and disease control rate.

Patients 18 years or older with an expected survival duration of 12 months or longer, histopathologically confirmed locally advanced unresectable or metastatic urothelial carcinoma, and no prior systemic therapy for locally advanced or metastatic disease were eligible for enrollment in the study. Additional eligibility criteria included having 1 or more measurable lesions per RECIST v1.1 guidelines; HER2 expression status of immunohistochemistry 1+, 2+, or 3+; an ECOG performance status of 0 or 1; and adequate cardiac, bone marrow, renal, hepatic, and coagulation functions.

Those with major surgery within 4 weeks of study entry or active central nervous system metastases were ineligible for study entry.

“We look forward to the excellent performance of [disitamab vedotin] in subsequent studies, which should provide a better decision-making basis for clinicians, bring more benefits to patients, and reshape the global treatment landscape of urothelial carcinoma,” Guo concluded.¹

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. May 12, 2025. Accessed May 13, 2025. https://tinyurl.com/msvmx7fk
2. A study of RC48-ADC combined with toripalimab for first-line treatment of urothelial carcinoma. ClinicalTrials.gov. Updated December 18, 2023. Accessed May 13, 2025. https://tinyurl.com/23h2xtkm