Acceleron is halting development of its cancer candidate dalantercept after topline results showed it failed the Phase II DART trial assessing the protein therapeutic in renal cell carcinoma (RCC).

Dalantercept plus axitinib missed the study’s primary endpoint of showing a statistically significant increase in progression-free survival (PFS) compared with placebo plus axitinib in advanced RCC patients, Acceleron acknowledged.

The median PFS for dalantercept plus axitinib was 6.8 months, compared with 5.6 months for placebo plus axitinib. Dalantercept plus axitinib did not decrease the rate of disease progression or death, Acceleron added.

DART enrolled 131 patients with advanced RCC—of which 58 patients were randomized to dalantercept plus axitinib, while 61 patients were randomized to placebo plus axitinib.

In the key secondary endpoint for the study—PFS for patients who received two or more prior systemic anticancer therapies—the median PFS for dalantercept plus axitinib was 8.1 months, compared with 7.0 months for placebo plus axitinib, a 22% improvement.

Worse, the confirmed objective response rate for placebo plus axitinib was 25%, compared with 19% for dalantercept plus axitinib.

“We are disappointed by the results given the need for new agents that improve outcomes for patients with advanced RCC,” Acceleron president and CEO Habib Dable said yesterday in a statement.

DART generated more favorable safety data, showing that the frequency of Grade 3 or higher adverse events (AEs) regardless of causality was 59% for dalantercept plus axitinib, and 64% for placebo plus axitinib. The frequency of serious AEs of any grade regardless of causality was considered similar for the dalantercept plus axitinib (29%) and placebo plus axitinib (26%) study arms.

Part 1 of DART was a dose-escalation study of dalantercept plus axitinib, designed 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 was a randomized, double-blind study of 130 patients with advanced RCC who have progressed following treatment with a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor. Patients may have also received prior mechanistic target of rapamycin (mTOR) therapy and/or immunotherapy.

Dalantecept is designed to inhibit angiogenesis by preventing bone morphogenetic protein-9 (BMP9) from interacting with activin receptor-like kinase 1 (ALK1), thus inhibiting ALK1 signaling.

Dable said Acceleron would focus instead on developing lead clinical candidate luspatercept with partner Celgene. Luspatercept is under study across multiple Phase III and Phase II studies as a treatment for myelodysplastic syndromes, beta-thalassemia, and myelofibrosis.

The company also plans to focus, Dable added, on developing ACE-083 across two neuromuscular diseases, facioscapulohumeral (FSH) muscular dystrophy and Charcot-Marie-Tooth disease.

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