Top-line results from the MONET1 pivotal Phase III trial evaluating motesanib (Amgen, Millennium: The Takeda Oncology Company and Takeda Pharmaceutical Company Limited), an investigational, orally-administered small molecule antagonist of VEGF (Vascular Endothelial Growth Factor) receptors 1, 2, and 3, platelet-derived growth factor receptors and stem cell factor receptor, administered in combination with paclitaxel and carboplatin in 1,090 patients with advanced non-squamous non-small cell lung cancer (NSCLC) show that the trial did not meet its primary objective of demonstrating an improvement in overall survival (OS) (hazard ratio 0.90, 95% CI 0.78 ? 1.04, p=0.14).

MONET1 (MOtesanib NSCLC Efficacy and Tolerability Study) is a Phase III, multicenter, randomized, placebo-controlled, double-blind trial that enrolled more than 1,000 men and women with NSCLC. Patients were randomized to receive either paclitaxel (200 mg/m2 IV Q3W), carboplatin (target AUC of 6 mg/mL x min IV Q3W), and motesanib (125 mg PO QD) or paclitaxel, carboplatin, and placebo. The primary endpoint of the study was OS, and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), association of placental growth factor with OS, duration of response, and safety and tolerability.

Commenting on the trial results, Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen said: “We are disappointed with the results from this trial, but look forward to further analysis of the data which may ultimately help inform future research in this area.”

“We thank the patients, caregivers, and investigators for their participation and engagement in the clinical evaluation of motesanib worldwide,” said Nancy Simonian, M.D., chief medical officer, Millennium. “These disappointing results support the need for new treatments to address the unmet need in advanced non-squamous NSCLC.”

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Overall, the adverse event profile for motesanib was consistent with that seen in previous motesanib studies in NSCLC. Notable adverse events reported included hypertension, GI events (abdominal pain, diarrhea, nausea, and vomiting), gallbladder events (cholecystitis, gallbladder enlargement), fatigue, and hematological events (neutropenia, thrombocytopenia). Serious adverse events were more frequently reported in the motesanib arm.

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Safety Concerns
In 2008 enrolment of patient in the Phase III MONET1 trial was temporarily suspended following a safety data review of 600 patients by the study’s independent Data Monitoring Committee (DMC). At that time discontinuation was based on an observation of higher early mortality rates in the motesanib group compared to the placebo group. esults will be submitted for presentation at an upcoming medical congress. In addition, a higher incidence of hemoptysis was also observed

The observations were consistent with data seen with some other anti-VEGF therapies and appeared to constitute a class effect of these types of agents.

Detailed results will be submitted for presentation at an upcoming medical congress.

For more information:

NCT00460317 – MONET1-MOtesanib NSCLC Efficacy and Tolerability Study.

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