Memorial Sloan Kettering Cancer Center (MSK) announced today that the U.S. Food and Drug Administration (FDA) has approved the oral MEK inhibitor drug cobimetinib (Cotellic^®) for the treatment of adult patients with the family of blood diseases known as histiocytic neoplasms (HN). These diseases include Erdheim-Chester disease, Rosai-Dorfman disease, and Langerhans cell histiocytosis. Cobimetinib is an oral inhibitor of MEK1 and MEK2, currently approved to treat melanoma.

The approval was granted based on data collected by MSK in collaboration with Genentech, a member of the Roche Group, from a single-institution phase 2 trial of single-agent cobimetinib for adults with histiocytic disorders. A rarity in the world of cancer research, the clinical trial that led to the approval was conducted solely at MSK.

This work builds upon the approval of vemurafenib (Zelboraf^®) in 2017 for the treatment of Erdheim-Chester disease, a type of histiocytosis. Vemurafenib targets the BRAF V600E mutation found in more than half of histiocytosis cases and was the first targeted therapy to be approved based on a basket trial, a novel tumor-agnostic clinical trial design pioneered at MSK.

“The approval of cobimetinib represents the collective hard work of several years of investigation by many MSK researchers. There have been tremendous advances in the field of rare cancers as a result of research and trials conducted at MSK, and this approval is an excellent example of a practice-changing outcome,” said Eli L. Diamond, MD, neuro-oncologist and neurologist at MSK and principal investigator of the trial. “There has always been an unmet need for patients with histiocytosis, and we are thrilled that with this approval, these patients will now have access to a viable treatment option.”

Histiocytosis is a family of blood diseases that affect both children and adults. These rare diseases are estimated to affect approximately 1 to 2 out of 200,000 people each year. The disease can infiltrate any part of the body, but most often presents in the brain. Before now, available treatment options for most adults with HN were limited and associated with poor long-term tolerance. Doctors at MSK care for more adults with histiocytosis than any other hospital in the United States.

In October 2019, the FDA announced Breakthrough Therapy Designation to cobimetinib for MEK inhibition in HN, based on a trial published in Nature in March 2019 by a team of MSK researchers led by Dr. Diamond; Omar Abdel-Wahab, MD, hematologic oncologist and Director of the Center for Hematologic Malignancies at MSK; and David Hyman, MD, former Chief of the Early Drug Development Service at MSK. The team used genetic sequencing test MSK-IMPACT^®, created by the Department of Pathology at MSK, to determine patients’ mutations.

“Until now, no standard therapy has existed for the 50% of histiocytosis patients without the BRAF V600E mutation,” said Dr. Abdel-Wahab. “The research pioneered at MSK has led to a viable treatment option for adult patients who harbor this mutation. Looking ahead, we are working on advancing treatment options for pediatric patients with histiocytosis as we have done in adults.”