A first-in-class JAK/ROCK inhibitor, Rovadicitinib in patients with myelofibrosis who were refractory or relapsed or intolerant to Ruxolitinib: A single-arm, multicenter, open-label, phase Ib study.

Patients with myelofibrosis (MF) who were relapsed or refractory, or intolerant to Ruxolitinib, have limited effective treatment options, and the outcome after discontinuation of Ruxolitinib is poor. Rovadicitinib (TQ05105) is a first-in-class, oral, small-molecule Janus kinase (JAK)/Rho-associated kinase (ROCK) inhibitor. Rovadicitinib has demonstrated significant clinical benefits in MF patients for spleen responses and reduced symptom burden. Here, we report safety and efficacy from a single-arm, multicenter, open-label, phase Ib study evaluating Rovadicitinib in MF patients resistant or intolerant to prior Ruxolitinib (NCT06388759). Between August 1, 2022, and September 05, 2023, patients were assessed for eligibility, and 9 patients were enrolled. The median duration of prior Ruxolitinib exposure was 40.6 months. At a median Rovadicitinib exposure of 12.5 months, the most common grade ≥3 treatment-emergent adverse event was thrombocytopenia (33.3 %). No report of a bleeding event and only one of 9 patients (11.1 %) permanently discontinued Rovadicitinib treatment. The spleen volume response rate (≥35 % spleen volume decrease from baseline to end of cycle 6 [EOC6]) was 25.0 %. Symptom response rate (≥50 % reduction from baseline to EOC6 in total symptom score on the modified Myelofibrosis Symptom Assessment Form) was 37.5 %. This study suggests that patients with MF who are intolerant or resistant to Ruxolitinib or other JAK inhibitors might achieve significant clinical benefit after treatment with Rovadicitinib. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT06388759.