MIAMI – Researchers are enrolling patients for part 2 of a phase 2 trial to compare dalantercept plus axitinib with axitinib alone for the treatment of advanced clear cell renal cell carcinoma (RCC), according to a study presented at the 14th International Kidney Cancer Symposium 2015 (IKCS).1

Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis, but concurrent targeting of ALK1 and vascular endothelial growth factor receptor (VEGFR) signaling results in dual angiogenic blockade and greater inhibition of tumor growth in preclinical studies of RCC tumor cells. Dalantercept  is an investigational protein that inhibits angiogenesis by preventing proteins BMP9 and BMP10 from interacting with ALK1, thereby inhibiting ALK1 signaling.

“In a completed phase 1 study in 37 patients with advanced solid tumors, dalantercept monotherapy demonstrated anti-tumor activity and the safety profile was generally non-overlapping with VEGFR TKIs,” Martin H. Voss, of Memorial Sloan Kettering Cancer Center in New York, NY, said during the poster presentation.

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Part 1 of the phase 2 evaluated the safety, tolerability, and preliminary activity of dalantercept every 3 weeks plus axitinib 5 mg twice daily in 29 patients with advanced RCC who had received at least 1 prior VEGFR tyrosine kinase inhibitors and no more than 3 prior treatments.

Results showed that the combination was associated with acceptable safety profile, an overall response rate of 25%, and a median progression-free survival of 8.3 months. The 12-month progression-free survival and overall survival rates in patients who had received dalantercept 0.9 mg/kg were 39% and 75%, respectively.

“These results compare favorably to the historical data with axitinib in TKI pre-treated RCC patients,” Dr. Voss noted.

In regard to safety, the most common adverse events were fatigue, diarrhea, dysphonia, peripheral edema, decreased appetite, epistaxis, hypertension, nausea, hand-foot syndrome, arthralgia, elevated creatinine, and cough.

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Now, researchers are enrolling patients in the part 2, multicenter, double-blind, phase 2 trial in order to randomly assign 130 patients with predominantly clear cell advanced RCC 1:1 to receive dalantercept plus axitinib or placebo plus axitinib. Patients are eligible if they have received 1 prior VEGF pathyway inhibitor, 1 prior mTOR inhibitor, and/or any number of previous immunotherapies. The primary endpoint is progression-free survival, with overall response rate, overall survival, and safety as secondary endpoints.


  1. Voss MH, Plimack E, Rini B, et al. The DART study: a phase 2 randomized double-blind study of dalantercept plus axitinib versus placebo plus axitinib in advanced clear cell renal cell carcinoma (RCC) [abstract]. BJU Int. 2015. doi: 10.1111/bju.13365.