This phase I/Ib trial seeks to find out the best dose, possible benefits and/or side effects of cabozantinib in combination with enfortumab vedotin in treating urothelial cancer that has spread to nearby tissues and lymph nodes (locally advanced) or other parts of the body (metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to a toxic agent called vedotin. Enfortumab attaches to nectin-4 tumor cells in a targeted way and delivers vedotin to kill them. Cabozantinib in combination with enfortumab vedotin may be safe and effective in treating locally advanced or metastatic urothelial cancer.
Histologically-documented urothelial carcinoma (squamous differentiation or mixed cell types allowed if urothelial carcinoma is present)
Metastatic disease or unresectable locally-advanced disease
Must have received prior treatment with a checkpoint inhibitor (CPI). A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor alone or with any other combination
Must either have prior treatment with platinum-containing chemotherapy or be ineligible at time of enrollment
Prior treatment with cabozantinib
Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs)
Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment
Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 2 weeks before first dose of study treatment