Date: 2011-06-04
Type of information:
phase: 3
Announcement: results
Company: Novartis (Switzerland
Product: INC424 (ruxolitinib)
Action mechanism: inhibitor of the JAK1 and JAK2 tyrosine kinases
Disease: myelofibrosis
Therapeutic area: Blood diseases - Cancer - Oncology
Country: Australia, Canada, Europe, USA
Trial
details: COMFORT-II is a randomized, open-label Phase III study of INC424 versus best available therapy (BAT) that enrolled 219 patients with primary myelofibrosis (MF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF) in 56 study locations in Europe. Two-thirds received INC424 (starting dose 15 or 20 mg twice daily) and one-third received BAT, which was administered at doses and schedules determined by the investigator. The primary endpoint for COMFORT-II was the proportion of patients achieving a reduction in spleen volume of 35% or more from baseline at week 48 as measured by MRI (or CT scan in applicable patients). Secondary endpoints included spleen size reduction at 24 weeks, duration of spleen size reduction, time to treatment response, change in bone marrow histomorphology, leukemia-free survival, progression-free survival and overall survival. Patients continue to receive INC424 therapy and to be followed to determine longer-term outcomes. COMFORT-II was conducted by Novartis in Europe.
COMFORT-I is the first Phase III study of INC424 and is a randomized, double-blind, placebo-controlled study that enrolled 309 patients with primary MF, PPV-MF or PET-MF, conducted by the collaboration partner Incyte Corporation in 89 study locations in the US, Canada and Australia. Half of patients received INC424 (starting dose 15 or 20 mg twice daily) and half received placebo. The primary endpoint was the proportion of patients achieving a reduction in spleen volume of 35% or more from baseline at week 24 as measured by MRI (or CT scan in applicable patients). Secondary endpoints included duration of maintenance of a 35% or greater reduction in spleen volume from baseline and the proportion of patients with 50% or more reduction in symptom improvement as measured by the modified Myelofibrosis Symptom Assessment Form electronic diary. COMFORT-I was conducted by collaboration partner Incyte Corporation in the US, Canada and Australia.
Latest
news: Novartis announced results from two pivotal Phase III studies demonstrating the effects of investigational Janus kinase (JAK) inhibitor INC424 (ruxolitinib) in treating patients with myelofibrosis, a blood cancer with limited treatment options. These data are being presented at the 47th American Society of Clinical Oncology (ASCO) annual meeting in Chicago. Novartis and Incyte have a worldwide collaboration and license agreement for INC424.
The Phase III trial COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) demonstrated that INC424 produced a volumetric spleen size reduction of 35% or greater in 28.5% of myelofibrosis patients compared to 0% of patients in the best available therapy arm at 48 weeks (p<0.0001). The trial also met a key secondary endpoint with 31.9% of INC424 patients demonstrating a 35% or greater volumetric spleen size reduction by week 24 compared to 0% in best available therapy patients (p<0.0001). Further, data showed a marked improvement in overall quality of life measures, functioning and symptoms relative to the best available therapy arm. COMFORT-I, conducted by Incyte, is a Phase III clinical trial comparing INC424 to placebo at 24 weeks. Results showed that 41.9% of myelofibrosis patients who received INC424 achieved at least a 35% reduction in spleen volume at 24 weeks from baseline compared to 0.7% of patients in the placebo arm (p<0.0001). COMFORT-I also met key secondary endpoints with statistical significance, including improvement of debilitating symptoms and demonstrating clinically relevant durations of spleen size reduction.
