Astex Pharmaceuticals said it may license out its Phase II-stage anticancer candidate amuvatinib (MP-470), but the announcement of suboptimal data from an ongoing Phase II trial means the firm isn’t going to put any more effort into continuing development of the drug in-house.
Amuvatinib is a small molecule multi-targeted tyrosine kinase inhibitor designed to inhibit mutant c-KIT and PDGFalpha, and disrupt DNA repair through what is likely to be a Rad51-based mechanism. The reported Phase II Escape study was evaluating amuvatinib in combination with platinum (etoposide) therapy in patients with small cell lung cancer.
The Simon 2-stage trial design had as its primary object in stage 1 of excluding the statistical probability with 90% confidence that adding amuvatinib to platinum therapy resulted in a less than 10% response rate in platinum-refactory small-cell lung cancer patients. However, while a number of patients on combination therapy demonstrated stable disease, the response evaluation by RECIST criteria showed a 9.5% response rate (two partial responses in the 21 evaluable patients in the first stage).
“While some clincial activity was observed, the Escape study response rate in stage 1 fell short of fully meeting our prespecified primary endpoint,” states Mohammad Azab, M.D., Astex’ CMO. “Consistent with our corporate strategy to move into advanced clinical stages only those agents that meet our prespecified primary endpoints in the clinical proof-of-concept stage, we decided to discontinue the internal development of this program.”
The firm notes that in a previously completed Phase Ib trial combining amuvatinib with carbopaltin and etoposide, responses were observed in patients with a range of tumor types including small-cell lung and neuroendocrine tumors.
Astex is exploiting its fragment-based drug discovery platform Pyramid™ to identify and develop small molecule drugs, primarily against cancer. The platform combines biophysical techniques including X-ray crystallography, nuclear magnetic resonance spectroscopy, and calorimetry, with fragment library design and computational methodologies.
The firm’s marketed drug Dacogen (decitabine) is a DNA hypermethylating agent approved in the U.S. and over 30 markets worldwide for the treatment of myelodysplastic syndromes. Dacogen is partnered with Eisai in North America, and Janssen-Cilag and affiliates in all other global territories. Regulatory filing for the drug as a treatment for acute myelogenous leukemia is under review in the EU. Astex’ in-house and partnered pipeline includes clinical-stage compounds against a range of cancer types.