Disitamab vedotin (DV) plus toripalimab (T) in unresectable locally advanced or metastatic urothelial carcinoma (la/mUC): Long-term outcomes from a phase Ib/II study

BackgroundThe outcomes of platinum-based chemotherapy as a standard of care for la/mUC remain poor, with median progression-free survival (PFS) and OS of 6.3 and 16.1 months (m). DV+T has demonstrated robust tumor response and PFS benefits, allowing the update of longer survival analyses. In the prior analysis (cutoff date Nov 18, 2022), the median PFS was 9.2m, and the 24-m survival rate was 63.2%. With a longer follow-up, we presented the OS analysis and other outcomes.MethodsRC48-C014 is a phase Ib/II investigator-initiated trial to evaluate the safety and efficacy of Disitamab Vedotin combined with Toripalimab in la/mUC. Eligible patients (pts) had histologically confirmed unresectable la/mUC who were cisplatin-ineligible without any systemic treatment or progressed on at least one-line systemic chemotherapy. The study comprised dose escalation and expansion of DV(1.5 or 2.0 mg/kg) in combination with T (3.0 mg/kg) once every 2 weeks. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), PFS, OS, and biomarker analysis.ResultsA total of 41 pts were enrolled. 25(61%) pts were cisplatin-ineligible and 16(39%) were post-chemotherapy. 38 (92.7%) pts with HER-2 expressing (≥ 1+) and 13 (31.7%) with PD-L1 positive (CPS≥10) were seen in the baseline immunohistochemistry test. At the data cutoff on Mar 01, 2024, 20 deaths occurred. With 34.14m of a median follow-up, the median OS was 33.05m (95% CI: 16.49-NE). The 24-m and 36-m survival rates were 60.0% and 47.7% respectively. The median PFS was 9.33m (95%CI: 5.75-11.17). The confirmed ORR was 75.0%, and the median duration of response was 8.61m (95%CI: 7.16-16.82). Consist with prior analysis, the most common treatment-related adverse events (TRAE) ≥Grade 3 were gamma-glutamyltransferase increased (12.2%), asthenia (9.8%), hypertriglyceridaemia (7.3%), and alanine aminotransferase increased (7.3%). The most common immune-related AE were rash (19.5%) and interstitial lung disease (12.2%).ConclusionsThese results represented robust response and notable OS benefits with manageable safety in long-term follow-up with DV+T, continuing to support DV+T as a promising treatment for la/mUC.Clinical trial identificationNCT04264936.Legal entity responsible for the studyRemeGen Co., Ltd.FundingRemeGen Co., Ltd.DisclosureL. Mao: Financial Interests, Institutional, Financially compensated role: MSD, Novartis, Shanghai Junshi, BioSciences; Financial Interests, Institutional, Research Funding: MSD. X. Wang: Financial Interests, Personal and Institutional, Advisory Board: Oriengene. J. Guo: Financial Interests, Personal and Institutional, Advisory Board: MSD, Roche, Pfizer, Bayer, Novartis, Simcere, Shanghai Junshi, BioSciences, Oriengene. X. Sheng: Financial Interests, Personal and Institutional, Speaker’s Bureau: Pfizer, Novartis, BeiGene, Junshi Pharmaceuticals, RemeGen. All other authors have declared no conflicts of interest.