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CRLX101 combination fails to extend PFS in patients with renal cell carcinoma
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A phase 2 trial designed to evaluate CRLX101 in combination with bevacizumab for the treatment of patients with advanced renal cell carcinoma failed to extend PFS, according to data released by the agent’s manufacturer.
The randomized, multicenter trial included 115 patients with renal cell carcinoma who progressed after two or three prior lines of therapy.
Patients received CRLX101 (Cerulean Pharma) in combination with bevacizumab (Avastin, Genentech) or investigator’s choice standard-of-care therapy. The investigator choices included axitinib (Inlyta, Pfizer), bevacizumab, everolimus (Afinitor, Novartis), pazopanib (Votrient, Novartis), sorafenib (Nexavar, Bayer), sunitinib (Sutent, Pfizer) and temsirolimus (Torisel, Pfizer).
Patients who received CRLX plus bevacizumab demonstrated no significant difference in median PFS compared with those who received investigator’s choice of therapy (3.7 months vs. 3.9 months; HR = 1.25; 95% CI, 2-5.4). Independent radiological review showed a higher overall response rate among patients assigned investigator’s choice (14% vs. 5%), although the difference was not statistically significant.
“We are disappointed with this outcome and will undertake a thorough analysis of the data to understand why CRLX101 plus bevacizumab underperformed compared to the results we saw in an earlier investigator-sponsored trial,” Christopher D. T. Guiffre, president and CEO of Cerulean, said in a company-issued press release.
The combination of CRLX101 and bevacizumab appeared safe and well tolerated, with a tolerability profile consistent with that observed in prior studies.
Complete data from the trial will be submitted for presentation at an upcoming medical conference.
“This outcome did not support our hypothesis that targeting hypoxia inducible factor (HIF) in combination with VEGF inhibitor in renal cell carcinoma, a HIF-overexpressing tumor type, would be beneficial, so we will not pursue HIF as a target going forward,” Guiffre said. “We will continue to focus on the potent topoisomerase 1 inhibition of CRLX101’s payload, camptothecin, in topoisomerase 1-sensitive tumors. Our combinations with weekly paclitaxel and olaparib (Lynparza, AstraZeneca) are examples of ongoing trials that leverage CRLX101’s topoisomerase 1 inhibition in combination with chemotherapies and DNA damage repair agents.”