Amgen, Takeda and Millennium update on phase 3 trial of Motesanib in non-small cell lung cancer

Amgen and Millennium: The Takeda Oncology Company, a subsidiary of Takeda Pharmaceutical Company Limited , today announced that enrollment in the Phase 3 MONET1 trial evaluating motesanib (AMG 706) in combination with paclitaxel and carboplatin for the first-line treatment of advanced non-small cell lung cancer (NSCLC) has been temporarily suspended following a planned safety data review of 600 patients by the study's independent Data Monitoring Committee (DMC). Motesanib is part of a broad co-development program between Amgen and Takeda.

The DMC recommended that enrollment in the study, which allowed both squamous and non-squamous NSCLC patients, be suspended based on an observation of higher early mortality rates in the motesanib group compared to the placebo group. In addition, the DMC recommended that the patients with squamous NSCLC immediately discontinue motesanib therapy based on an observation of a higher incidence of hemoptysis. The DMC did not recommend discontinuation of motesanib therapy for the patients with non-squamous NSCLC. The DMC will review updated data after three months.

Amgen, in collaboration with Takeda Bio Development Center, is implementing both of the DMC's recommendations and notifying worldwide regulatory agencies, including the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMEA), and Japan's Pharmaceuticals and Medical Devices Agency (PMDA), as well as motesanib clinical investigators.

"While we are disappointed in this outcome, it is consistent with data seen with some other anti-VEGF therapies and appears to constitute a class effect of these types of agents," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "Patient safety is our top priority, hence we have acted quickly to implement the recommendations of the DMC. Working with our development partner, Takeda, we will continue to evaluate the therapeutic potential of motesanib in non-squamous NSCLC and metastatic breast cancer, as well as in other solid tumors."

"NSCLC continues to be an area where new and effective therapies are needed. We look forward to the follow up recommendations from the DMC in order to chart the best path forward for the development of this molecule," said Nancy Simonian, M.D., chief medical officer, Millennium: The Takeda Oncology Company.

MONET1 (Motesanib NSCLC Efficacy and Tolerability Study) Trial Design

This Phase 3, multicenter, randomized, placebo-controlled, double-blind trial has enrolled 1,100 of 1,240 planned patients with advanced NSCLC. Patients with either squamous or non-squamous NSCLC were allowed in this study. Squamous NSCLC is a histological subtype of NSCLC and accounts for approximately one-third of the study population. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, objective response rate in patients with measurable disease, duration of response and safety. Patients were randomized 1:1 to receive carboplatin and paclitaxel administered every three weeks with or without 125 mg motesanib taken daily.

Co-developed by Amgen, Takeda Pharmaceutical Company, and Millennium: The Takeda Oncology Company, motesanib is an investigational, highly selective, oral agent that is being evaluated for its ability to inhibit angiogenesis by targeting vascular endothelial growth factor receptors 1, 2 and 3 (VEGFR1-3). It is also under investigation for its potential direct anti-tumor activity by targeting a family of proteins called tyrosine kinases, including platelet-derived growth factor receptor (PDGFR), and stem cell factor receptor (c-kit), two proteins involved in cell proliferation.

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