AbstractRuxolitinib has demonstrated efficacy in patients with myelofibrosis (MF). However, substantial number of patients may not respond after 3–6 months of treatment or develop resistance over time. In this phase 2 trial, patients with a current diagnosis of intermediate or high‐risk MF who either had an inadequate splenic response or spleen regrowth after ruxolitinib treatment were enrolled. All patients received jaktinib 100 mg Bid. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR 35) at week 24. The secondary endpoints included change of MF‐related symptoms, anemic response, and safety profile. From July 6, 2021, to January 24, 2022, 34 ruxolitinib‐refractory or relapsed patients were enrolled, 52.9% (18 of 34) were DIPSS intermediate 2 or high risk. SVR 35 at week 24 was 32.4% (11 of 34, 95% CI 19.1%–49.2%) in all patients and 33.3% (6 of 18, 95% CI 16.3%–56.3%) in the intermediate 2 or high‐risk group. A total of 50% (8 of 16) transfusion‐independent patients with hemoglobin (HGB) <100 g/L at baseline had HGB elevation ≥20 g/L within 24 weeks. Furthermore, 46.4% (13 of 28) of patients had a ≥ 50% decrease in the total symptom score (TSS 50) at week 24. The most common grade ≥3 treatment‐emergent adverse events (TEAEs) were thrombocytopenia (32.4%), anemia (32.4%), and leukocytosis (20.6%). In total, 13 (38.2%) of 34 patients had serious adverse events (SAE), of which drug‐related SAEs were found in 5 patients (14.7%). These results indicate that jaktinib can be a promising treatment option for patients with MF who have either become refractory to or relapsed after ruxolitinib treatment.