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Lung Cancer Drug Motesanib Fails Late-Stage Trial

Future looks shaky for VEGF receptor antagonist

The phase III MONET-A study has failed to meet its primary endpoint in patients with stage IV non-squamous non–small-cell lung cancer (NSCLC) who were randomly assigned to treatment with motesanib (Takeda Pharmaceutical Company) in combination with paclitaxel and carboplatin compared with placebo plus paclitaxel and carboplatin. As a result, the study has been terminated.

Motesanib is an investigational, orally administered small-molecule antagonist of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3; of platelet-driven growth factor receptors; and of stem-cell factor receptors.

MONET-A was a multinational, randomized, placebo-controlled, double-blind study examining the efficacy and safety of motesanib when administered with paclitaxel and carboplatin in 401 patients with stage IV or recurrent non-squamous NSCLC and no prior chemotherapy, molecularly targeted therapy, or immunotherapy (for metastatic disease).

The trial’s primary efficacy endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), the objective response rate (ORR), the duration of response, safety, and the pharmacokinetics of motesanib and its metabolites when the compound was administered in combination with paclitaxel and carboplatin.

The MONET-A study was initiated in patients in Japan, South Korea, Taiwan, and Hong Kong after the completion of a previous phase II trial, MONET1, which compared motesanib, paclitaxel, and carboplatin with chemotherapy alone in patients with non-squamous NSCLC. Although the MONET1 trial did not meet its primary objective of demonstrating a statistically significant improvement in OS, a pre-planned analysis revealed significant and consistent findings in the Asian population for ORR, PFS and OS, providing the rationale for the MONET-A trial.

All is not lost for the oncology pipeline at Takeda, however. Last week the company announced results from a phase III study (TOURMALINE-MM1) of the company’s blood cancer drug ixazomib. The trial results showed that ixazomib, the first oral proteasome inhibitor, met its primary endpoint of improving PFS in patients with relapsed or refractory multiple myeloma. Patients who received ixazomib plus lenalidomide and dexamethasone lived without their disease worsening for a significantly longer period compared with patients who received placebo plus lenalidomide and dexamethasone. The results were from an interim analysis.

The future of motesanib looks shaky because of the two failed trials and because of cardiac events seen in some patients participating in the studies.

Sources: Takeda; Feb 17; and BioSpace; February 17, 2015.

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