799MO - The primary results from a randomized double-blind phase II study of rovadicitinib versus hydroxyurea in patients with myelofibrosis

Background

Rovadicitinib (TQ05105), a novel JAK/ROCK inhibitor, showed meaningful clinical activity in patients (pts) with MF in a phase I/Ib study (NCT04339400). This phase II study aimed to assess the efficacy and safety of rovadicitinib (R) compared to hydroxyurea (H) in pts with intermediate-2 or high-risk MF.

Methods

Pts aged ≥18 with PMF, post-PV MF or post-ET MF, DIPSS Int-2 or high risk, palpable splenomegaly, and no prior treatment with a JAK inhibitor were enrolled and randomly assigned (2:1) to receive R 15 mg bid plus H placebo or H 0.5 g bid plus R placebo, stratified by DIPSS risk status (Int-2 or high risk). The primary endpoint was the proportion of pts whose reduction of at least 35% in spleen volume (SVR35) at week 24 compared with baseline.

Results

Between November 11, 2021, and April 27, 2023, 107 pts were enrolled, 72 pts receiving R and 35 receiving H. 73.61% (R) and 71.43% (H) pts were JAK2 V617F positive. The median spleen volume was 2092 cm³ (R) and 1666 cm³ (H). The patient baseline characteristics in the two arms were basically balanced. As of October 15, 2023, the SVR35 rates at week 24 were 58.33% for R vs. 22.86% for H (p=0.0006). R showed a consistent spleen response benefit over H across all subgroups analyzed. The TSS50 rates at week 24 were 61.11% for R vs. 45.71% for H (p=0.136). The best spleen response rates were 63.89% vs. 31.43% (p=0.0017), and the best TSS50 rates were 77.78% vs. 54.29% (p=0.0136). The most common grade ≥3 hematological TEAEs were anemia (28.89% [R] vs. 60.00% [H]), thrombocytopenia (20.00% vs. 17.14%), decreased lymphocyte count (7.78% vs. 11.43%), leukopenia (4.44% vs. 17.14%), and neutropenia (4.44% vs. 17.14%). Most common nonhematological TEAEs were hyperuricemia (26.67% vs. 17.14%), weight gain (26.67% vs. 14.29%) and blood creatinine increased (17.78% vs. 2.86%), predominantly of grade 1 or 2. TEAEs leading to treatment discontinuation occurred in 7.78% of R and 14.29% of H.

Conclusions

Rovadicitinib demonstrated significant clinical benefits compared to hydroxyurea in MF pts for spleen response or improved symptom response. Rovadicitinib may be a new treatment option for myelofibrosis pts.

Clinical trial identification

NCT05020652.

Editorial acknowledgement

Legal entity responsible for the study

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Funding

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Disclosure

D. Ding, D. Wang: Financial Interests, Personal and Institutional, Affiliate: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. All other authors have declared no conflicts of interest.