NCT02439346

Phase I Dose Escalation and Expansion of Oral BAY 1143269 in Combination With Intravenous Docetaxel

An Open-label, Non-randomized, Multicenter Phase I Study to Characterize the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Maximum Tolerated Dose of Oral MKNK1 Inhibitor BAY 1143269 Given Alone or in Combination With Intravenous Docetaxel in Subjects With Advanced Solid Tumors

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: Bayer · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), and/or recommended Phase II dose (RP2D) of oral BAY 1143269 given alone or in combination with intravenous (IV) docetaxel in subjects with advanced solid tumors.

Detailed description

BAY 1143269 is a potent and selective, orally administered novel inhibitor of mitogen-activated protein kinase interacting serine/threonine-protein kinase 1 (MKNK1). MKNK1 activity is essential for the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), which promotes the synthesis of oncogenic proteins, inhibits apoptosis, and helps tumor cells survive under stress. Increased p-EIF4E levels were found in tumor tissues from cancer patients. MKNK also functions as a mediator of pro-inflammatory cytokine production. Established anti-mitotic drugs such as vinca alkaloids, taxanes, or epothilones activate the spindle assembly checkpoint (SAC), a key surveillance mechanism that monitors the attachment of spindle microtubules to the kinetochores of the chromosomes during pro-metaphase and halts the transitions to anaphase until all chromosomes are bi-oriented, fully attached, and correctly tensed at the metaphase plate. These antimitotic drugs destabilize or stabilize the spindle microtubules and cause mitotic arrest. Prolonged arrest in mitosis forces a cell either into a mitotic exit without cytokinesis or into a mitotic catastrophe leading to cell death. MKNK1 inhibitors allow cell apoptosis and increase tumor death. The combination of taxane and MKNK1 inhibitor can ultimately delay tumor progression and may provide a useful anticancer therapeutic approach. This study will attempt to answer the following questions: * What is the maximum tolerated dose (MTD) of BAY 1143269 when given alone or in combination with docetaxel? * What is the safety profile and pharmacokinetics of BAY1143269 when given at the MTD? * What are the adverse events of BAY 1161909 when given at different dose levels with docetaxel?

Conditions

• Medical Oncology

Interventions

Type	Name	Description
DRUG	BAY1143269 tablet	BAY 1143269 5 mg or 25 mg tablet. Each treatment cycle will last 21 days.

Timeline

• Start date: 2015-06-15
• Primary completion: 2017-03-27
• Completion: 2017-04-24
• First posted: 2015-05-08
• Last updated: 2018-03-07

Locations

4 sites across 2 countries: United States, United Kingdom

Regulatory

• FDA-regulated drug study