Fedratinib (FEDR) in myelofibrosis (MF) patients previously treated with ruxolitinib (RUX): A reanalysis of the JAKARTA-2 study.

Abstract

7057 Background: MF is a life-threatening MPN for which RUX is the only approved treatment (Tx) option. Patients (pts) who are relapsed/refractory (R/R) or intolerant to RUX have a particularly high unmet medical need. FEDR is an oral selective JAK2 inhibitor active against wt and mut JAK2. The JAKARTA-2 study demonstrated ≥35% spleen volume responses (SVR) in pts resistant or intolerant to RUX per investigator assessment. This JAKARTA-2 reanalysis employs a more stringent definition of RUX failure than used in the previous analysis. Methods: Adult pts previously treated with RUX with intermediate or high-risk primary, post-PV, or post-ET MF, palpable splenomegaly, ECOG PS ≤2, and platelet counts ≥50 × 109/L received FEDR 400 mg QD in continuous 28-day cycles. The primary endpoint was spleen volume response rate (SVRR): ≥35% SVR from baseline (BL) at cycle 6 end per blinded central review of MRI/CT scans. A key secondary endpoint was symptom RR (≥50% decrease in total symptom score from BL). Results: 79/97 enrolled pts (81%) met the more stringent criteria for RUX R/R (n=65, 82%) or intolerance (n=14, 18%). Median BL spleen volume was 2946 mL (~14× normal). Median prior RUX Tx duration was 11.5 mo (range 1.0–62.4). Median number of FEDR Tx cycles was 7 (1–20). SVRR with FEDR was 30% (95% CI 21, 42). KM estimated median spleen response duration was not estimable (95% CI 7.2 mo, NE). Symptom RR was 27%. Safety was consistent with prior reports. Conclusions: FEDR provided clinically meaningful reductions in splenomegaly and symptom burden in pts with MF who met more stringent criteria for R/R or intolerance to RUX. Clinical trial information: NCT01523171. [Table: see text]