Pathological complete response and potential for bladder preservation by theranostic instillation therapy targeting CXCR4 in combination with systemic chemotherapy: The Bladder BRIDGister experience.

• DOI: 10.1200/jco.2025.43.5_suppl.691
• Publication Date: 2025-02-18T14:42:46Z
• Authors: Ralph M. Wirtz; Enno Storz; Melanie von Brand...; Frank Friedersdorff; Dimitri Barski; Thomas Otto; Michael Waldner; Johannes Graff; Elke Veltrup; Roland Hake; Sebastian Eidt; Jenny Roggisch; Constantin Rieger; Stefan Koch; Thorsten Ecke; Lukas Greifenstein; Axel Heidenreich; Richard P Baum
• Keywords: Systemic therapy

691 Background: Patients with muscle invasive urothelial carcinoma (MIBC) achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NACT) have improved prognosis. Previously we did show that luminal tumors respond better to NACT (Ecke et al 2022), while chemoresistant express radioligand targets CXCR4 and FAP. First-in-Human treatment of resistant T4 MIBC using two cycles Lu 177 FAP combined one cycle pembrolizumab results in durable (Baum al, submitted). The objective this study was eradicate naïve T2a limited probability by adding intravesical instillation into the bladder before first justify subsequent adopted clinical trials. Methods: A reference cohort (n=100) for subtype classification constructed. RNA from FFPE tissues extracted, relative gene expression non-luminal target were analyzed RT-qPCR. tissue initial TURB patients under evaluation therapy accordingly individual mRNA added cluster analysis determine level. PET/CT Imaging Ga 68 performed selected patients. In case tumor specific, high uptake instilled week initiation ddMVAC. Response evaluated control resections TURB. Results: pT2 G3 patient elevated level RT-qPCR validated immunohistochemistry, who predicted be unresponsive NACT, therapy. Subsequent whole body proved specific excluded nodal involvement as well distant metastasis. Thereafter 4GB applied via catheter Radio-Ligand-Therapy (iRLT) followed three a starting planned second iRLT Intravesical revealed response, no being visible anymore. including absence malignancy only inflammatory immune reaction left after RLT based NACT. Conclusions: Combination molecular vitro diagnostics identifies risk expression, exhibit vivo are amenable intensified systemic ddMVAC treatment. First promising approaches part phase 1 / 2 trials within Bladder BRIDGister group ultimate goal preservation pCR combination therapies.