Safety and Activity of G-202 in Patients With Clear Cell Renal Cell Carcinoma That Expresses PSMA

Epithelial tumors, including clear cell renal cell carcinoma (RCC), have the ability to grow to only a finite size in the absence of vascularization. RCC is characterized as a highly-vascularized tumor and inhibiting angiogenesis has the potential to impair tumor growth, including growth of RCC. Therapeutic targeting of integral biological pathways in RCC, including those involving VEGF and mTOR, has produced robust clinical effects and revolutionized the treatment of metastatic RCC. These approaches offers significant clinical benefit and sequential use of these agents has become the empirical standard of care. However, complete or durable responses are uncommon and resistance develops after a median interval of 6-15 months. This raises the pressing clinical need for additional therapeutic approaches for patients with metastatic clear cell RCC. The purpose of this study is to investigate the approach of targeted delivery of cytotoxic chemotherapy with G-202 in patients with advanced, refractory RCC. This study is based on prodrug tumor targeting, in which an inactive form of a toxic agent is administered systemically and gets activated in specific locations in the body, resulting in higher concentrations of the cytotoxic form at the tumor location. G-202 is a prodrug that is activated by PSMA in the blood vessels of tumors, but not normal tissue; once activated, G-202 leads to disruption of intracellular calcium levels and subsequent induction of apoptosis. Thus, G-202 is expected to bring about cell death in RCC and destroy the blood supply of RCC tumors. This single-arm, open-label Phase II clinical trial will evaluate the safety and activity of G-202 in patients with RCC that expresses PSMA.