Acceleron Pharma, Inc., a biopharmaceutical company developing protein therapeutics for cancer and orphan diseases, has started a phase II study of dalantercept, a novel angiogenesis inhibitor that targets the activin receptor-like kinase 1 (ALK1) pathway. The phase II study is a two-part, randomized study of dalantercept in combination with axitinib (Inlyta, Pfizer), a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, to treat patients with metastatic renal cell carcinoma (RCC).

Acceleron, its partners, and collaborators have now initiated seven phase II studies across three of Acceleron’s programmes – dalantercept (ACE-041), sotatercept (ACE-011), and ACE-536 – since November of 2012.

“Many patients with renal cell carcinoma respond to treatment with a VEGF inhibitor yet their disease subsequently progresses,” said Michael B Atkins, MD, deputy director, Georgetown Lombardi Comprehensive Cancer Centre, Georgetown University Medical Centre. “We are optimistic that combining two therapies with distinct anti-angiogenesis mechanisms, a VEGF inhibitor and dalantercept, an ALK1 signaling inhibitor, can provide a more effective and durable antitumor response in these patients.”

“Angiogenesis is known to be a key factor in the development and progression of renal cell carcinoma,” said Matthew Sherman, MD, chief medical officer of Acceleron. “Dalantercept, in combination with a VEGF inhibitor, may inhibit angiogenesis more completely which could lead to improved outcomes in RCC patients. Acceleron is excited by the potential of dalantercept and is committed to a broad development programme for this promising molecule.”

The clinical trial is designed as two-part study in patients with metastatic renal cell carcinoma. Part 1 is a dose-escalation study of dalantercept in combination with axitinib to evaluate the safety and tolerability of the combination as second line treatment. Part 2 is an open-label, randomized study to determine whether treatment with dalantercept in combination with axitinib prolongs progression free survival (PFS) compared to treatment with axitinib alone.

Dalantercept (ACE-041) is an investigational protein therapeutic that inhibits angiogenesis by preventing BMP9 and BMP10, proteins in the TGF-ß superfamily, from interacting with activin receptor-like kinase 1 (ALK1), a cell-surface receptor found on proliferating vascular endothelial cells. Dalantercept inhibits ALK1 signaling, which is required for the development of mature, functional vasculature. In a phase I clinical study in patients with advanced-stage tumours, dalantercept was generally well-tolerated and also exhibited signs of clinical activity, including patients with objective response and prolonged stable disease. In addition to the phase II study in patients with metastatic RCC, dalantercept is also in phase II clinical trials for monotherapy treatment of patients with advanced head and neck cancer (NCT01458392), endometrial cancer (NCT01642082), and ovarian cancer (NCT01720173).

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, accounting for approximately 85 per cent of cases. RCC is the sixth most common cancer diagnosis in men and an increase in incidence has been reported worldwide. Over 200,000 new patients are diagnosed with RCC worldwide each year. Treatment for advanced stages of RCC, which represents about 20 per cent of patients, consists of immunomodulators, vascular endothelial growth factor (VEGF) receptor inhibitors, and/or mammalian target of rapamycin (mTOR) kinase inhibitors. Despite multiple products approved to treat RCC, resistance to treatment remains a serious clinical challenge.

Acceleron is committed to discover, develop, manufacture and commercialize novel protein therapeutics for orphan diseases and cancer.