The combination of bevacizumab and an investigational nanoparticle-drug conjugate known as CRLX101 failed to improve outcomes in metastatic renal cell carcinoma (RCC) compared with standard of care, according to a new phase II trial.
CRLX101 contains camptothecin, an inhibitor of topoisomerase I as well as of HIF1-alpha and HIF2-alpha. To date, CRLX101 has been investigated in more than 400 patients in various malignancies, both in combination or as monotherapy; a phase Ib/II trial combined with bevacizumab showed it was well tolerated and active in metastatic RCC, which overexpresses HIF.
Thomas Hutson, DO, PharmD, of the Charles A. Sammons Cancer Center at Baylor University Medical Center in Dallas, presented results of the new phase II study. A total of 115 patients were randomized to either the CRLX101/bevacizumab arm or a standard of care arm. All patients had received two to three prior lines of therapy; the standard of care group received physician’s choice of several drugs including axitinib, everolimus, sunitinib, and others.
Most patients (90%) had clear cell histology, and almost all had received two prior lines of therapy. Axitinib was the most commonly selected standard of care agent, followed by bevacizumab and everolimus.
The study drug did not yield an improvement in progression-free survival, which was the primary endpoint. CRLX101 patients had a median progression-free survival of 3.7 months, compared with 3.9 months with standard of care, for a hazard ratio of 1.25 (P = .822). Hutson said a progression-free survival of around 4 months is what one would expect in a refractory group of patients.
There was also “no appreciable difference” with regard to objective response rate, Hutson said. There were no complete and two partial responses with CRLX101, and two complete and four partial responses with standard of care. Hutson said that fatigue, nausea, and constipation were common in the experimental arm, but the grade 3/4 toxicity profiles were actually very similar across the two groups.
“There are no future plans for evaluation of the combination in RCC,” Hutson said, based on the negative results from this study. However, there are ongoing trials using CRLX101 in topoisomerase I–sensitive malignancies including ovarian cancer and gastrointestinal tumors.