Cabozantinib + Enfortumab Vedotin

PRIMARY OBJECTIVES: I. To determine the recommended phase II dose (RP2D) of cabozantinib s-malate (cabozantinib) and enfortumab vedotin 1.25 mg/kg on days 1, 8 and 15 of a 28-day cycle based on safety and tolerability. (Phase I dose escalation) II. To evaluate the ongoing safety and tolerability of cabozantinib and enfortumab vedotin in a dose expansion cohort. (Phase Ib dose expansion) SECONDARY OBJECTIVES: I.

Obtain preliminary evidence of anti-tumor activity of the combination of cabozantinib and enfortumab vedotin by assessing the objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. II. Progression-free survival (PFS). III. Overall survival (OS). IV. Disease control rate by RECIST v1.1. EXPLORATORY OBJECTIVES: I. To assess the pharmacokinetic (PK) profile of cabozantinib during treatment with enfortumab vedotin. II.

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.

Live record on ClinicalTrials.gov →

• 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
• Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
• Tumor tissue samples must be available for submission prior to initiation of study treatment or patient must be willing to undergo repeat tumor biopsy

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.