Background: Currently, ruxolitinib is the only marketed Janus kinase inhibitor (JAKi) for pts with MF in China, which demonstrated symptomatic and splenic benefit with increased cytopenias. However, at least 50% of pts develop resistance or intolerance to ruxolitinib in the long-term follow up, for whom life expectancy is largely reduced. There are few therapeutic options after ruxolitinib failure. Jaktinib, an oral novel JAK and AVCR1 inhibitor showed promising activity in Jaki-naïve pts with intermediate or high risk MF with mild side effects. Here we present the results of jaktinib in MF pts who were refractory or relapsed to prior ruxolitinib therapy. Methods: Pts who had primary or post-ET/PV MF and were previously treated with ruxolitinib for at least 3 months and with either inadequate efficacy response (defined as < 10% spleen volume reduction [SVR] by MRI/CT or < 30% decrease in spleen size by palpation from baseline) or spleen regrowth to < 10% SVR or < 30% decrease in spleen size from baseline following an initial response were recruited to receive jaktinib 100 mg twice daily. The primary endpoint was the proportion of pts with SVR ≥ 35% from baseline (SVR35) at week (wk) 24, measured by MRI/CT images and assessed by Independent Review Committee. Secondary endpoints included the best spleen response rate (defined as achieving SVR35 at any time), the proportion of pts with ≥ 50% reduction in MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), improvement of anemia and safety. Results: A total of 34 pts were enrolled. The median duration of previous ruxolitinib treatment was 18.6 months (range 3.4-70.1). The median baseline TSS was 19.5 (range 1-55), hemoglobin (Hb) was 101.5 g/L (range 61-149), and platelets was 159×10⁹/L (range 66-951). 11 pts (32.4%) achieved SVR35 at wk 24. The best spleen response rate was 38.2% (13/34). The median time to achieve the first SVR35 was 8.1 weeks, and the median duration of response was not reached. At wk 24, 13 pts (46.4%) achieved a ≥ 50% improvement in TSS from baseline. Of 16 transfusion-independent pts with Hb ≤ 100 g/L at baseline, 8 (50.0%) had a ≥20 g/L Hb increase by wk 24. Of 6 pts who required RBC transfusion at baseline, 2 had a 50% decrease in RBC infusion by wk 24. The median jaktinib exposure time was 231 days (range 96-371). 23 pts (67.6%) had one or more grade ≥3 treatment emergent adverse events (TEAEs). The most common grade ≥3 TEAEs were anemia (32.4%, n = 11), thrombocytopenia (32.4%, n = 11), leukocytosis (20.6%, n = 7) and leukopenia (11.8%, n = 4). Treatment discontinuation due to TEAEs occurred in 2 pts (5.9%). A dose reduction or temporary interruption due to TEAEs were reported in 9 pts (26.5%). Conclusions: MF pts who were refractory/relapsed to ruxolitinib attained substantial spleen response, and reduction in MF-related symptom burden with jaktinib, which could be a new option for MF pts who have failed ruxolitinib. Clinical trial information: NCT04851535.