Novartis Announces Results From Global Phase III RATIFY Or CALGB 10603 Trial

(RTTNews) - Novartis (NVS) announced results from the global Phase III RATIFY or CALGB 10603 clinical trial. In the study, adult patients under 60 years of age with newly-diagnosed FLT3-mutated acute myeloid leukemia (AML) who received the investigational compound PKC412 (midostaurin) plus standard induction and consolidation chemotherapy experienced a 23% improvement in overall survival (OS) (hazard ratio [HR] = 0.77, P = 0.0074) compared to those treated with standard induction and consolidation chemotherapy alone.

The median OS for patients in the PKC412 (midostaurin) treatment group was 74.7 months (95% confidence interval [CI]: 31.7, not attained), versus 25.6 months (95% CI: 18.6, 42.9) for patients in the placebo group.

The trial evaluated the addition of either PKC412 (midostaurin) or placebo to daunorubicin/cytarabine in the induction phase, followed by high-dose cytarabine in the consolidation phase; patients who achieved complete remission after consolidation chemotherapy continued treatment with PKC412 (midostaurin) or placebo as a single agent for up to one year.

In addition to meeting the primary endpoint of OS, event free survival (EFS, defined as the earliest death, relapse or no complete response within 60 days of the start of induction therapy) was significantly higher in the PKC412 (midostaurin) treatment group versus the placebo group [HR = 0.79, P = 0.0025 and median of 8.0 months (95% CI: 5.14, 10.6) vs. 3.0 months (95% CI: 1.9, 5.9)].

No statistically significant differences were observed in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events (AEs). A total of 37 deaths were reported, with no difference in treatment-related deaths observed between group.

"The RATIFY study, in partnership with the Alliance for Clinical Trials in Oncology, reflects our relentless pursuit to develop targeted therapies that can improve and extend people's lives," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "Based on the results of this trial, we plan to move forward with global regulatory submissions for PKC412 (midostaurin) in the first half of 2016."

In order to help identify patients who may have a FLT3 mutation and potentially benefit from treatment with PKC412 (midostaurin), Novartis said it is collaborating with Invivoscribe Technologies, Inc. who will lead regulatory submissions for a companion diagnostic.