ASCO 2024 | Phase Ib/II trial of 177Lu-girentuximab with cabozantinib and nivolumab in clear cell RCC

Eric Jonasch, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses a Phase Ib/II trial (NCT05663710) of combination 177Lu girentuximab plus cabozantinib and nivolumab in treatment naive patients with advanced clear cell renel cell carcinoma (RCC). Despite recent advancements with the combination of nivolumab plus cabozantinib, Complete response (CR) remains rare. Leveraging the cGAS-STING pathway activated by radiation-induced DNA damage, the study investigates the potential synergy between 177Lu girentuximab, a targeted peptide receptor radionuclide therapy, and immunotherapy. The trial aims to enroll up to 100 treatment-naive ccRCC patients to evaluate the safety and efficacy of this combination regimen. The hypothesis is that 177Lu girentuximab-induced DNA damage will potentiate the STING pathway, synergizing with nivolumab and cabozantinib to enhance CR rates. Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and overall survival. Pre/post-treatment PET scans and biopsies will assess activated T cell infiltration. This innovative approach offers a promising strategy to improve outcomes in ccRCC. This interview took place during the 2024 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.

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