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Company Ends Development of Lung Cancer Drug
Response rate only 9.5% for amuvatinib in phase II trial (Sept. 21)
Astex Pharmaceuticals, Inc., based in Dublin, Calif., announced on September 21 that clinical development of amuvatinib (MP-470), a multi-targeted tyrosine kinase inhibitor that inhibits mutant forms of the proto-oncogene c-Kit and platelet-derived growth factor receptor-alpha (PDGFR-alpha) and disrupts DNA repair, likely through suppression of the homologous recombination protein Rad51, has been discontinued.
Amuvatinib was being investigated in the phase II ESCAPE (TrEatment of Small Cell lung cancer with Amuvatinib in combination with Platinum Etoposide) study. The study used a two-stage design, with the primary objective in stage 1 of excluding the statistical probability with 90% confidence that the drug has less than a 10% response rate in patients with platinum-refractory small-cell lung cancer (SCLC).
Response evaluation by RECIST criteria showed two partial responses in the 21 evaluable patients in stage 1 of the study (a 9.5% response rate). No new safety issues were identified. Several patients had prolonged stable disease. The study results will be presented at a future scientific meeting.
"This clinical proof-of-concept amuvatinib trial was designed in two parts to define clinical activity and to confirm clinical benefit and safety in combination with chemotherapy," said James Manuso, PhD, the company’s chairman and chief executive officer. "We have decided to end the clinical development of amuvatinib despite the favorable safety and preliminary clinical activity we observed in the first stage of this phase II trial and in the earlier phase Ib trial in combination platinum/etoposide-based chemotherapy. We will consider the possibility of licensing the compound to any partners who would be interested in its further development."
Amuvatinib is an oral multi-targeted tyrosine kinase inhibitor that inhibits the mutant forms of c-Kit and PDGFR-alpha. It also disrupts DNA repair, likely through suppression of the homologous recombination protein Rad51 — an important survival pathway in many human cancers. In vitro and in vivo data have demonstrated the synergy of amuvatinib with DNA-damaging agents, including etoposide and doxorubicin. In the amuvatinib clinical development program, more than 200 subjects were exposed to at least one dose of amuvatinib. In a phase Ib clinical study of amuvatinib in combination with carboplatin and etoposide, responses in SCLC (neuroendocrine and other tumor types) were observed.
For more information, visit the Astex Pharmaceuticals Web site.