This trial was designed to evaluate the efficacy and safety of RX‐0201 in combination with everolimus in eligible subjects with mRCC. Eligible criteria included confirmed histologic or cytologic evidence of renal cancer with a clear cell component, measurable disease as defined by the RECIST criteria, and received at least one course of therapy with a VEGFR inhibitor and progressed within 6 months of the planned first dose of on study treatment. In Phase 1, subjects were enrolled at increasing doses of RX-0201, which was delivered via continuous IV for 14 days, in combination with 10 mg/day everolimus in a modified 3+3 design. The target dose of RX-0201 identified in Phase 1 was 250 mg/m2/day, which was further evaluated in Phase 2 of the study. The primary objectives included the safety and efficacy at the recommended Phase 2 dose and the primary endpoint was progression-free survival benefit for at least 4.5 months.
There were 11 patients (7 males) with mRCC treated with RX-0201 (250 mg/m2/day) + everolimus (10 mg/ day) in Phase 2 of the trial. The median age was 64 years (range 53-72), ECOG performance status at screening was 0 to 1, and 55% of patients had received ≥ 3 prior therapies. The median progression-free survival was 4.9 months. Four subjects had stable disease after 6 months of treatment. The most frequent related adverse events (> 15%) were Grade 1/2 epistaxis, Grade 3 fatigue, and Grade 1/2 nausea and G1 vomiting.
The authors noted that recruitment to this study was significantly affected by a change in the standard of care for advanced RCC due to the approval new therapies (nivolumab, cabozantinib, and lenvatinib + everolimus). Therefore, enrollment to an everolimus alone arm was stopped early in the study due to a change in the standard of care. The historical PFS for everolimus is 4.0 months and the PFS in this combination therapy study was 4.9 months. They concluded that in this mRCC population with extensive prior treatment, RX‐0201 in combination with everolimus was safe and tolerable.
Clinical trial information: NCT02089334
Presented by: Neeraj Agarwal, University of Utah Huntsman Cancer Institute, Salt Lake City, UT
Co-Authors: Sumanta K. Pal, Richard C. Lauer, Gurkamal S. Chatta, Sanjay Goel, Parminder Singh, Srinath Sundararajan, Callie Heaton, Christine Peterson, Ely Benaim, Scott T. Tagawa; City of Hope, Duarte, CA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM; Virginia Mason Medical Center, Seattle, WA; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; University of Arizona Cancer Center, Tuscon, AZ; University of Arizona Cancer Center, Tucson, AZ; Rexahn Pharmaceuticals, Inc., Rockville, MD; Division of Hematology & Medical Oncology, Meyer Cancer Center, Department of Urology, Weill Cornell Medical College & New York-Presbyterian Hospital, New York, NY
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA