A phase 1/2 study to assess peptidomimetic carbonic anhydrase IX imaging and therapy with 68 GaGa-DPI-4452 and 177 LuLu-DPI-4452 in patients with advanced clear cell renal cell carcinoma and other solid tumors.

TPS569 Background: The diagnostic and clinical benefit of the peptidomimetic carbonic anhydrase IX (CA IX) -binding theranostic pair 68 GaGa-DPI-4452/ 177 LuLu-DPI-4452 is being investigated in an ongoing, multicenter, Phase 1/2 study (NCT05706129). The study design comprises 5 parts; First-in-Human Part A assessed safety, pharmacokinetics, biodistribution and dosimetry of a single intravenous injection of 185 MBq 68 GaGa-DPI-4452 in various solid tumors including clear cell renal cell carcinoma (ccRCC), and has been completed (Hofman et al, 2024). Theranostic Parts B and C will determine one or more recommended Phase 2 dose(s) (RP2D) and evaluate preliminary antitumor activity of 177 LuLu-DPI-4452 in patients with advanced ccRCC, and potentially in other tumor types. Major objectives of the additional imaging Parts D and E are to evaluate the diagnostic concordance between 68 GaGa-DPI-4452 PET and histopathology in patients with indeterminate renal mass (IDRM) (Part D) and to explore 68 GaGa-DPI-4452 uptake in different tumor types (Part E). Methods: In the Phase 1 dose escalation (Part B), patients with ccRCC are currently enrolled and undergo 68 GaGa-DPI-4452 imaging as part of screening to confirm and quantify tumor CA IX expression, i.e., eligibility for 177 LuLu-DPI-4452 therapy. Optional 68 GaGa-DPI-4452 PET scans may be conducted during treatment alongside conventional tumor assessments. Approximately 64 evaluable patients with ccRCC and potentially other tumor types will be included to establish the maximum tolerated dose and/or one or more RP2D for each tumor type. Subsequently, the preliminary antitumor activity of 177 LuLu-DPI-4452 monotherapy at RP2D will be evaluated in tumor-specific Phase 2 expansion cohorts (Part C). Part D is open for recruitment with the goal to include approximately 36 patients with IDRM. Patients receive a single dose of 68 GaGa-DPI-4452 at 185 MBq (±20%) followed by whole body PET/CT scans at 1 and 3 hours post-infusion. Confirmation of tumor lesions as ccRCC is based on mean and maximum standard uptake values. Tumor tissue samples are collected during radical or partial nephrectomy, biopsy or other invasive diagnostic methods as per local standard practice within 90 days. Clinical trial information: NCT05706129 .