Date: 2017-06-12
Type of
information: Results
phase: 2
Announcement: results - discontinuation of development
Company: Acceleron Pharma (USA - CA)
Product: dalantercept and axitinib
Action
mechanism:
- protein/tyrosine kinase inhibitor/VEGFR inhibitor. Dalantercept is a first-in-class angiogenesis inhibitor with a mechanism distinct from VEGF inhibition. Dalantercept is a soluble form of the activin receptor-like kinase 1 (ALK1) that binds to the TGF-? superfamily members BMP9 and BMP10 and prevents these proteins from signaling through ALK1. ALK1 is expressed on activated blood vessel cells and plays critical roles in the formation and maturation of blood vessels. Dalantercept inhibits ALK1 signaling, which is required for the development of mature, functional vasculature.
- Axitinib is an oral and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3.
Disease: advanced renal cell carcinoma
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
- The Phase 2 DART clinical trial is a two-part study in patients with advanced renal cell carcinoma. Part 1 is a dose-escalation study of dalantercept plus axitinib to evaluate the safety and tolerability of the combination in patients whose disease has progressed following one to three lines of prior therapy. Part 2 is a randomized, double-blind study of 130 patients with advanced renal cell carcinoma who have progressed following treatment with a VEGF receptor tyrosine kinase inhibitor. Patients may have also received prior mTOR therapy and/or immunotherapy. (NCT01727336)
Latest
news:
- • On June 12, 2017, Acceleron Pharma announced that the DART Phase 2 study of dalantercept plus axitinib did not achieve its primary endpoint in advanced renal cell carcinoma. The primary efficacy endpoint of the study was to demonstrate a statistically significant increase in progression-free survival for treatment of dalantercept plus axitinib versus placebo plus axitinib in advanced RCC patients.
- The DART study enrolled 131 patients with advanced renal cell carcinoma. The efficacy data are based on the All-Treated Set (ATS) which is defined as all randomized patients who received any study drug (n=119) as of the database cutoff. In the ATS, 58 patients were randomized to dalantercept plus axitinib and 61 patients were randomized to placebo plus axitinib.
- The median PFS for dalantercept plus axitinib was 6.8 months versus 5.6 months for placebo plus axitinib. Dalantercept plus axitinib did not decrease the rate of disease progression or death (HR 1.11, two-sided 95% CI [0.71, 1.73], one-sided p-value 0.67).
- The key secondary endpoint for the study was PFS for patients who received two or more prior systemic anti-cancer therapies. In this analysis, the median PFS for dalantercept plus axitinib was 8.1 months versus 7.0 months for placebo plus axitinib (HR 0.78, two-sided 95% CI [0.33, 1.87], one-sided p-value 0.29). The confirmed objective response rate (ORR) for dalantercept plus axitinib was 19% versus 25% for placebo plus axitinib (p-value 0.43, Cochran-Mantel-Haenszel test).
- The safety data are based on the 119 ATS patients. The frequency of Grade 3 or higher adverse events (AEs) regardless of causality were similar overall in the dalantercept plus axitinib (59%) and the placebo plus axitinib (64%) study arms. The frequency of serious AEs of any grade regardless of causality were also similar in the dalantercept plus axitinib (29%) and the placebo plus axitinib (26%) study arms. The AEs associated with dalantercept were consistent with those previously observed.
- Based on the lack of efficacy, Acceleron Pharma is discontinuing the development of dalantercept.
Is
general: Yes
