The development of dalantercept, an anaplastic lymphoma kinase 1 (ALK1) inhibitor, has been halted by the manufacturer, Acceleron, due to the failure of dalantercept to significantly improve progression-free survival (PFS) compared to the tyrosine kinase inhibitor, axitinib (Inlyta) in a phase II clinical trial. It was hoped dalantercept would improve PFS by stopping the formation of the blood vessels tumours need to enable them to grow and spread. VEGF inhibitors, such as pazopanib and sunitinib, already halt tumour blood vessel formation, but dalantercept has a different mechanism of action to these drugs.

The trial included 131 people with advanced renal cell carcinoma, who were randomised to receive either dalantercept plus axitinib, or axitinib plus placebo. Dalantercept did not meet the primary PFS endpoint of the trial. The dalantercept plus axitinib combination resulted in a median PFS of 6.8 months, versus 5.6 months for the axitinib plus placebo regimen; the difference was not statistically significant.

In addition, the dalantercept plus axitinib combination failed to reduce the rate of disease progression or death, and the combination was suboptimal against placebo in terms of objective response rate and PFS in patients who had received two or more prior systemic cancer therapies. Median PFS for the combination compared with placebo was 8.1 months versus 7 months in these patients, and the objective response rate for the combination was 19% versus 25% for placebo.

Read more here

Read the article in Cure here