Tremelimumab + Durvalumab(MEDI4736)+ Belinostat in Urothelial Carcinoma

Description

PRIMARY OBJECTIVES:

I. To assess the recommended phase 2 dose of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab alone in advanced urothelial carcinoma. (Phase 1A) II. To assess the ongoing safety of belinostat in combination with durvalumab in patients with advanced urothelial carcinoma. (Phase 1B)

SECONDARY OBJECTIVES:

I. To assess the efficacy of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab in patients with advanced urothelial carcinoma.

EXPLORATORY OBJECTIVES:

I. To assess the mechanism of action of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab.

II. To explore possible mechanisms of treatment resistance. III. Determine the feasibility of establishing patient-derived xenografts from tumor cells collected from enrolled subjects at baseline, and progression to better explore mechanisms of response and resistance. IIII. To explore possible biomarkers predictive of treatment benefit.

OUTLINE: This is a dose-escalation study of belinostat.

Patients receive durvalumab intravenously (IV) over 30 minutes on day 1. Patients also receive tremelimumab IV over 60 minutes on day 1 of cycle 1. Beginning cycle 2, patients receive belinostat IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.