Novartis announced that The New England Journal of Medicine (NEJM) published data for PKC412 (midostaurin) demonstrating an overall response rate, defined as a major or partial response, of 60% (95% confidence interval [CI], 49-70%; P<0.001) in patients with advanced systemic mastocytosis (SM). The median duration of response for all responders in the primary efficacy population was 24.1 months (95% CI, 10.8-not estimated [NE].
Advanced SM is a rare disease characterized by the accumulation of abnormal mast cells, a type of white blood cell, in the bone marrow, liver, spleen and other organs, leading to organ damage. It is also characterized by frequent activating mutations of the KIT gene.
The pivotal Phase II study, CPKC412D2201, was the largest and longest-running prospective trial ever conducted in this rare disorder. Jason Gotlib, MD, of Stanford University School of Medicine and Stanford Cancer Institute, served as lead author of the study, which enrolled 116 people with advanced SM. Eligibility and responses were reviewed by a Study Steering Committee and 89 patients were eligible for inclusion in the primary efficacy population. Patients received single-agent, oral PKC412 (midostaurin) until disease progression or unacceptable toxicity. Results demonstrated a median overall survival (OS) of 28.7 months (95% CI, 18.1-NE).
"These data show clear disease and symptom improvement with oral midostaurin treatment across a range of study participants who were reflective of the heterogeneity of this disease," said Professor Andreas Reiter, Department of Hematology and Oncology, University Hospital Mannheim of the University of Heidelberg, Germany and senior author of the study. "If approved, midostaurin will offer patients a much needed treatment option."
"Patients with advanced SM are part of a very small, highly underserved community that has suffered from a lack of medical innovation for many years," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "Novartis is proud to have developed a treatment that shows benefit for these patients, and is now working with regulatory authorities to make midostaurin available as quickly as possible."
PKC412 (midostaurin) is an investigational, oral, multi-targeted kinase inhibitor that was recently granted Breakthrough Therapy Designation for adults with newly-diagnosed FLT3-mutated acute myeloid leukemia (AML) by the US Food and Drug Administration (FDA). PKC412 (midostaurin) additionally has orphan drug status in the EU and US for both AML and mastocytosis.
