Phase II study results of response rate of PKC 412 (midostaurin) in systemic mastocytosis published in New England journal of Medicine- Novartis

Novartis announced that The New England Journal of Medicine (NEJM) published data for PKC 412 (midostaurin) demonstrating an overall response rate, defined as a major or partial response, of 60% in patients with advanced systemic mastocytosis (SM). The median duration of response for all responders in the primary efficacy population was 24.1 months. The pivotal Phase II study, CPKC412D2201, was the largest and longest-running prospective trial ever conducted in this rare disorder.

Patients received single-agent, oral PKC 412 until disease progression or unacceptable toxicity. Results demonstrated a median overall survival (OS) of 28.7 months. Improvements in both bone marrow mast cell burden and serum tryptase levels � a marker for mast cell burden � were seen in 78% of patients, and were associated with disease regression. The most frequent side effects were gastrointestinal. With the exception of nausea and vomiting, all 32 symptoms self-reported with the Memorial Symptom Assessment Scale significantly decreased with treatment. Quality of life, assessed by the 12-item Short Form Health Survey (SF-12), was also significantly increased with PKC412 treatment, compared to baseline values: improvement was shown by a 26% increase in mental health scores and a 29% increase in physical health scores.

The Phase II study results are also reinforced in a letter published in the same issue of NEJM by the French Reference Centre of Mastocytosis (CEREMAST) regarding a compassionate use program for PKC 412 in advanced SM6. After a median follow-up time of 18.5 (3-36) months, the overall response rate to treatment was 71%. After a similar follow-up time, the OS rate was 42.7%, compared with 14.9% in a matched historic control group. A more than twofold higher risk of death was also observed in the control group. The most frequent side effects were nausea/vomiting in 89% of patients (leading to failure/discontinuation in 18%), lymphocytopenia in 61% without opportunistic infection and photosensitivity in 25%. The authors concluded that PKC412 is effective in advanced SM.

See: "Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis." Gotlib J, Kluin-Nelemans HC, George TI, et al. New Engl J Med. 2016;374(26):2530-2541.