A Phase 2 Study to Assess the Safety and Efficacy of Cobimetinib in Refractory Langerhans Cell Histiocytosis, LCH-Associated Neurodegenerative Disease, and Other Histiocytic Disorders

Summary and Objectives

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm, which means it is a disease where certain bone marrow-related immune cells grow abnormally and cause inflammation in the body, which can damage tissues in areas like bone, skin, and organs. In the past, treatment options have been limited, and are often associated with high toxicity. With advances in understanding of LCH biology, new targeted or cellular therapies may ultimately be more effective and/or safer than high-dose chemotherapy for patients who fail to respond to initial treatments.

Cobimetinib is a MEK inhibitor, which is a type of targeted therapy that blocks the activity of certain enzymes responsible for cell survival, division, and growth. Supported by the success of targeted therapies in studies of similar context, this study seeks to evaluate the safety and efficacy of Cobimetinib as a less toxic treatment option for certain histiocytic disorders.

Eligibility criteria

In addition to a few criteria that could prevent participation, there are criteria participants must meet including but not limited to the following:

• For groups 1-3, participants must be at least 6 months old; group 4 participants must be at least 21 years old.
• Must be able to take an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Must have a biopsy-confirmed qualifying diagnosis
• Must have failed at least initial line of therapy for patients with LCH
• Participants with LCH-associated neurodegenerative disease must have confirmed radiologic or clinical progression within the past 3 months
• Must have adequate organ function and performance levels as determined by the study protocol
• Female patients of childbearing potential require a negative urine or serum pregnancy test and must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment.
• Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug.
• Must not continue taking certain protocol-identified medications/therapies
• Must not have received Cobimetinib previously
• Various protocol-identified comorbidities (active or history of) could prevent participation in this study

Clinicaltrials.gov Study Details >