Jaktinib in MF: Updates from ASCO and EHA 2023

Jaktinib, an inhibitor of Janus kinase-1, -2, and -3, has shown promising spleen reduction properties and is therefore being evaluated in multiple clinical trials for the treatment of myelofibrosis (MF).¹

The latest updates from three trials of jaktinib for MF were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) 2023 Hybrid Congress.^1–3 The MPN Hub is pleased to summarize key data from these presentations here.

The MPN Hub’s top picks for abstracts from EHA 2023, including a phase III study jaktinib versus hydroxycarbamide in patients with intermediate-2 or high-risk MF (ZGJAK016; NCT04617028), can be found here.

Study design

A summary of the intervention, study designs, and primary endpoints of the three trials included in this review are presented in Table 1.

Table 1. Summary of ZGJAK016, ZGJAK017, and ZGJAK006 trials*

Results

ZGJAK016: Jaktinib versus hydroxyurea in intermediate-2 and high-risk MF¹

A higher percentage of patients in the jaktinib arm reached spleen volume reduction ≥35% (SVR35) at both 12 weeks and 24 weeks in comparison with the hydroxyurea (HU) arm (Figure 1).

Figure 1. SVR35 rates at Week 12 and Week 24* 

*Adapted from Zhang.¹

Secondary endpoints included the total symptom score (TSS) response rate in both cohorts, defined as a ≥50% reduction in myeloproliferative neoplasm Symptom Assessment Form (MPN-SAF) TSS from baseline. At Week 24, 55.3% of patients achieved a TSS response rate compared with 34.8% in the HU arm. A summary of TSS response rates is shown in Figure 2.

Figure 2. TSS response rates* 

*Adapted from Zhang.¹

The best spleen response was 80.9% in the jaktinib arm compared with 26.1% in the HU arm. The maximum change in spleen volume from baseline was −46.59% and −18.5%, respectively.

Grade ≥3 treatment-emergent adverse events (TEAEs) were recorded in 51.1% of patients receiving jaktinib and 60.9% of those receiving HU. Key TEAEs of interest are outlined in Table 2.

Table 2. TEAEs in the jaktinib and hydroxyurea cohorts*

ZGJAK017 and ZGJAK006: Jaktinib in ruxolitinib intolerant and ruxolitinib R/R MF^2,3

At Week 24, SVR35 was achieved in 43.2% of patients intolerant to ruxolitinib and 32.4% of patients relapsed or refractory (R/R) to ruxolitinib. Primary endpoint data, best spleen response data, and the number of patients achieving a ≥50% improvement in TSS from baseline are shown in Figure 3.

Figure 3. Outcomes following treatment with jaktinib in patients who were R/R or intolerant to ruxolitinib* 

*Data from Zhang² and Zhang.³

TEAEs of Grade ≥3 occurred in 67.6% of ruxolitinib R/R patients and 60% of ruxolitinib intolerant patients. The most common TEAEs were hematologic, with thrombocytopenia being the most prevalent in both cohorts.

Conclusion

Jaktinib resulted in an overall improvement in splenomegaly in patients who were intolerant, relapsed, or refractory to ruxolitinib. A consistent spleen reduction was also observed in intermediate-2 and high-risk patients in comparison with HU. Safety outcomes were deemed tolerable by the researchers across all jaktinib cohorts, presenting a possible treatment option for these MF subgroups. However, it is notable that the ZGJAK017 and ZGJAK006 studies of ruxolitinib intolerant and R/R MF lacked a comparison arm with either standard-of-care treatment or placebo.