ASCO GU 2019: RENAVIV: Pazopanib with or without Abexinostat in Patients with Locally Advanced or Metastatic Renal Cell Carcinoma

San Francisco, CA (UroToday.com) Abexinostat (ABEX) is a potent, orally bioavailable pan-HDAC inhibitor. Pazopanib (PAZO) is a standard front line VEGF tyrosine kinase inhibitor (TKI) for the treatment of locally advanced or metastatic renal cell carcinoma (mRCC). A prior phase 1 study of PAZO +ABEX demonstrated durable anti-tumor activity in heavily pretreated RCC patients.1 Peripheral blood histone acetylation and HDAC expression were associated with treatment outcomes in this phase 1 study. The currently presented poster is of a phase 3 study designed to evaluate whether the addition of ABEX prolongs and reverses resistance to PAZO therapy for patients with RCC.

The study scheme is shown in Figure 1 (Clinical trial NCT03592472). The primary endpoint is progression-free survival. The secondary endpoints include progression-free survival by investigator assessment, overall survival, objective response rate, duration of response, response rate and duration of response in cross over patient’s population, patients reported outcomes/quality of life, and safety.

Figure 1 – Trial scheme:
UroToday ASCOGU2019 RENAVIV study2
There are also some planned correlative studies, involving peripheral blood mononuclear cells, and archived tumor tissue. The first patient enrolled was in October 2018.

Presented by: Rahul Aggarwal, MD, University of California, San Francisco, California

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan, at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

References:
  1. Aggarwal et al. Inhibiting Histone Deacetylase as a Means to Reverse Resistance to Angiogenesis Inhibitors: Phase I Study of Abexinostat Plus Pazopanib in Advanced Solid Tumor Malignancies. Journal of Clinical Oncology 35, no. 11 (April 10 2017) 1231-1239.