Target: MEK | Indication: Thyroid Cancer and NF1

Introduction / Brief Description

Selumetinib is an oral small-molecule MEK inhibitor invented by Array and licensed to AstraZeneca. AstraZeneca is responsible for development and commercialization of selumetinib. To date, Array has earned $26.5 million in up-front and milestone payments and is entitled to receive approximately $70 million (with $30 million specific for selumetinib) in potential additional development milestone payments and royalties on product sales.

MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of this pathway has been shown to occur in many cancers, in particular through mutations in BRAF, KRAS and NRAS.

Two registration trials are advancing with selumetinib in advanced cancer patients: differentiated thyroid cancer (ASTRA), and neurofibromatosis Type 1 (NF1).

Thyroid Cancer and NF1

The incidence of thyroid cancer is increasing in the United States, with over 64,300 new cases and almost 1,980 deaths projected in 2016. Most thyroid cancers can be treated successfully, with an overall five-year survival rate of 98%. However, even when therapy is successful the disease remains potentially lethal, with as many as 35% of thyroid cancers recurring. There is a significant unmet need for novel therapies to treat metastatic thyroid disease. Novel therapies that target the RAS/RAF/MEK/ERK pathway have a strong scientific rationale for activity in this disease, as thyroid cancers are often characterized by mutations in BRAF (approximately 39% of patients) and NRAS (approximately 7% of patients).

NF is a genetic disorder that can cause typically non-malignant tumors, or PNs, to grow on nerves throughout the body.  These tumors can be very disfiguring, painful and disabling.  Most tumors are
inoperable, while some patients undergo, often repeated surgical procedures.  NF1 also causes a number of other health issues, including deafness, blindness, learning disabilities, bone abnormalities and sometimes cancer. PNs exhibit the most rapid growth in young children, and therefore early intervention in children with growing PNs may result in the greatest clinical benefit. NF1, which appears in approximately one in 3,000 people, or 100,000 in the United States, has no cure. 


Clinical Trials

Trial Data
Trial Title
Program: Selumetinib (AZD6244)
Phase: 3
Status: Recruiting
Disease: Thyroid cancer
Sponsor: AstraZeneca
Trial Information: NCT01843062
Trial Title: Study Comparing Complete Remission After Treatment With Selumetinib/Placebo in Patient With Differentiated Thyroid Cancer (ASTRA)
Program: Selumetinib (AZD6244)
Phase: 2
Status: Recruiting
Disease: Neurofibromatosis Type 1
Sponsor: National Cancer Institute
Trial Information: NCT01362803
Trial Title: AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors
Program: Selumetinib (AZD6244)
Trial Information:
Trial Title: Other clinical trials


Selumetinib / Cancer



A Phase I study of the MEK1/2 inhibitor selumetinib in combination with first-line chemotherapy regimens for NSCLC

E. Dean, et al.

Selumetinib / Cancer


American Society of Clinical Oncology Meeting

A Phase I Study of the MEK1 Inhibitor Selumetinib (AZD6244) Hydrogen Sulfate in Children with Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PNs)

B. C. Widemann, et al.

Selumetinib / Cancer


Children’s Tumor Foundation’s Neurofibromatosis Conference

A Phase I Study of the MEK 1/2 Inhibitor AZD6244 (Selumetinib) in Children and Young Adults with Neurofibromatosis Type 1 (NF1) and Plexiform Neurofibromas (PN)

B. Widemann, MD, et al.

Selumetinib / Cancer


American Society of Clinical Oncology Annual Meeting

Phase II Study of Selumetinib vs Temozolomide in Patients with Advanced Uveal Melanoma (CTEP #8443)

R. D. Carvajal

Selumetinib / Cancer


The Lancet Oncology

Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study

J. Farley, et al.


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