ZGJAK002 trial: Efficacy and safety of jaktinib in patients with MF

Jaktinib, a Janus kinase, and activin A receptor type I inhibitor, is a deuterated form of momelotinib and has shown promising results for treating patients with myelofibrosis (MF), specifically in spleen volume reduction and symptom relief.

Here, we summarize a long-term follow-up of the ZGJAK002 trial (NCT03886415) published by Zhang et al.¹ in American Journal of Hematology assessing the safety and efficacy of jaktinib in Chinese patients with intermediate to high-risk MF.

Study design¹

• Phase II, open-label dose comparison trial 30.7 months after trial initiation
• Patients (N = 118) were assigned 100 mg jaktinib twice daily (BID, n = 66) or 200 mg jaktinib once daily (QD, n = 52)
• The primary endpoint was the proportion of patients with ≥35% decrease in spleen volume (SVR35) at Week 24.
• Secondary endpoints included total symptom score improvement by ≥50% (TSS50), improvement in anemia, and safety profile.

Key findings¹

• More patients achieved SVR35 with 100 mg BID vs 200 mg QD (Figure 1)
  • The proportion of patients achieving spleen volume reductions increased over time, indicating durable responses
• TSS50 improvements and hemoglobin levels were sustained in both groups from Week 48 to Week 120 in long-term follow-up results (Table 1).
• No further safety signals were identified in either cohort, common Grade ≥3 adverse events outlined in Table 1.

Table 1. Key long-term efficacy and safety data for jaktinib 100 mg BID and 200 mg QD regimens*

AE, adverse event; BID, twice daily; TSS50; total symptom score improvement by ≥50%; QD, once daily. *Adapted from Zhang, et al.1
	100 mg BID (n=66)	200 mg QD (n=52)
TSS50 (%)
Week 48	81.6	81.5
Week 120	63.6	81.0
Mean hemoglobin change (g/L)
Week 48	4.76	8.69
Week 120	0.25	0.25
Grade ≥3 AEs (%)
Anemia	15.2	21.2
Thrombocytopenia	15.2	11.5
Infectious pneumonia	10.6	1.9

• Median overall survival was not met by either cohort, with 36-month survival rates of 78.0% vs 73.6%, respectively
  • Deaths were reported in 18.2% and 25%, respectively

BID, twice daily; MF, myelofibrosis; QD, once daily; SVR35, spleen volume reduction ≥35%.
*Adapted from Zhang, et al.¹

Key learnings

Both 100 mg BID and 200 mg QD regimens of jaktinib demonstrated a sustained improvement in SVR35, anemia, and TSS50. However, a higher proportion of patients achieved SVR35 with 100 mg BID. Along with sustained elevation of hemoglobin levels and consistent safety profile, this long-term data supports further evaluation of 100 mg BID over 200 mg QD in patients with intermediate to high-risk MF who require a rapid spleen response.