Early detection of side effects in patients with metastatic melanoma receiving immune checkpoint inhibitors by investigation of CD8+ immune infiltrate with 89Zr crefmirlimab berdoxam PET.

TPS9601 Background: Immune checkpoint inhibitors (ICI) improved outcomes of patients (pts) with advanced melanoma. Nevertheless, a significant number have immune-mediated adverse event (iAE). Due to the impact on quality of life and other therapeutic options, early identification of pts with increased risk of iAE is needed. CD8 immuno-PET with 89 Zr crefmirlimab berdoxam (Zr-Df-IAB22M2C) has shown to be a specific tool to visualize CD8+ T cells mediating both anti-tumor immune response and inflammatory adverse effects rendering this an innovative evaluation method in the field of immuno-oncology. Methods: Trial design: Open-label, single-arm, single center study to determine if CD8+ T-cell infiltration evaluated by immune-PET provides diagnostic gain in early detection of severe iAE. Pts with irresectable stage III/IV melanoma receiving nivolumab + ipilimumab (NIVO+IPI) may be included. Primary objective: Feasibility of early detection of iAE by semiquantitative assessment of CD8+ T-cell infiltration using immune-PET. Secondary objectives: 1) Prediction of iAE using immuno-PET for semiquantitative assessment of CD8+ T-cell infiltration; 2) Correlation between CD8+ T-cell infiltration in metastasis and lymphoid organs and response. Baseline Imaging. To assess glucose metabolism in metastases, primary and secondary lymphatic organs 18 F FDG PET/CT (60 min p.i. 1.5 MBq/KG/BW) is performed on a high sensitivity PET/CT with large field of view (Siemens Vision Quadra). Immediately after PET/CT data acquisition, pts are injected with 89 Zr crefmirlimab berdoxam (37 MBq ±20%) and undergo immuno-PET/CT 24 hours p.i. to detect CD8+ T-cells in metastases and lymphoid organs. NIVO+IPI is administered immediately after completion of 89 Zr crefmirlimab berdoxam-PET/CT. Blood samples are taken for immune cell composition analysis, activation state, proteomic investigation (cytokine/chemokines) as well as metabolic profile. Therapy Phase Imaging: Three weeks after first ICI cycle and before second cycle, follow-up PET/CT are performed with both radiotracers 18 FFDG and 89 Zr crefmirlimab berdoxam following the identical protocol described above. Clinical trial information: EudraCT number - 2021-004328-13 .