The combination of Inlyta (axitinib) and dalantercept, an activin receptor–like kinase 1 (ALK1) signaling inhibitor appears promising in the treatment of advanced renal cell carcinoma (RCC) according to the results of a recently published Phase I clinical trial.1 According to investigators, 25% of RCC patients responded to treatment with the combination and this represents an improvement compared to treatment with Inlyta alone.
About Renal Cell Carcinoma
Each year in the United States, more than 61,000 people are diagnosed with kidney cancer. The most common type of kidney cancer is RCC, which starts in the lining of very small tubes (tubules) in the kidney. For people with advanced RCC (cancer that has spread to other parts of the body), targeted therapies can play an important role in treatment. Approximately 20-30% of patients with RCC will have metastases at diagnosis and as many as 40% will demonstrate metastasis after primary surgical treatment for localized RCC. With a 5-year survival rate ranging from 5-10%, the prognosis is poor and new treatments are needed.
Dalantercept is a protein that targets and inhibits the growth of new blood vessels essential for supplying the cancer with nutrients to grow. This process, called angiogenesis can be prevented by blocking certain proteins from interacting with activin receptor-like kinase 1 (ALK1), a cell-surface receptor found on growing endothelial cells essential for new blood vessel formation. By inhibiting the ALK1 signaling pathway, growth factor-induced angiogenesis necessary for tumor growth is inhibited, which may result in the inhibition of tumor cell proliferation and tumor cell death.
In the current clinical trail, called DART, dalantercept was administered along with Inlyta in 29 patients with advanced heavily pretreated RCC. All patients had received up to three prior therapies. None of the patients previously received Inlyta or an ALK1-directed therapy. Patients were treated with increasing doses of dalantercept subcutaneously every three weeks, and oral Inlyta twice daily, until disease progression or intolerance.
Overall 25% of patients experienced a partial response to treatment, 60% had stable disease and 14% had their disease progress during treatment. Fourteen patients experienced either partial response or stable disease for at least six months. Overall 40% of patients were progression free and 75% survived greater that one year from beginning treatment. Patients treated with the highest dalanterept dose experienced even greater time to cancer progression and improved survival.
The study authors concluded that dalantercept plus Inlyta demonstrated a favourable safety profile and clinically meaningful antitumor activity in a pre-treated population of patients with RCC. Additional clinical trials are ongoing evaluating dalantercept and Inlyta.
Reference: (Clin Cancer Res 2016 Dec 28. PMID: 28031424)
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