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. 2022 Nov 24;141(16):1954–1970. doi: 10.1182/blood.2022017423

Table 5.

Ongoing phase 3 trials in JAKi-exposed patients with MF

Agent
mechanism of action
Clinical trial characteristics Key inclusion criteria Definition of failure to first-line therapy Primary end point
Imetelstat (IME)
Telomerase inhibitor
IMpactMF/MYF3001
NCT04576156
IME vs BAT (excluded JAKis)
(estimated n = 320)
IME 9.4 mg/kg q21
DIPSS Int-2/high-risk symptomatic MF
PLT ≥75 × 109/L
Spleen length ≥5 cm below LCM or volume ≥450 cm3
≥6 mo of JAKi with no spleen/symptoms reduction
≥3 mo of JAKi at MTD with no spleen/symptoms reduction
≥3 mo of JAKi at MTD and relapsing splenomegaly
OS
Navitoclax (NAVI)
BCL-XL/BCL-2 inhibitor
TRANSFORM-2
NCT04468984
NAVI+RUX vs BAT, (included JAKis) (estimated n = 330)
NAVI 100 or 200 mg QD, based on PLT count
RUX at prior stable dose or 10 mg BID
DIPSS+ Int-2/high-risk symptomatic MF
PLT ≥100 × 109/L
Spleen length ≥5 cm below LCM or volume ≥450 cm3
≥6 mo of RUX, stopped for lack/loss or spleen response or for relapsed symptom control
≥6 mo of RUX, continued despite relapsed/refractory status
<6 mo of RUX, with progression/appearance of splenomegaly
≥1 mo of RUX at ≥15 mg BID to keep efficacy with RBC units need
SVR35 at 24 wk
Navtemadlin (NAVT)
MDM2 inhibitor
BOREAS
NCT03662126
NAVT vs BAT (excluded JAKi)
(estimated n = 385)
NAVT 240 mg QD d 1-7 of 28-d cycle
DIPSS Int/high-risk MF
PLT ≥50 × 109/L
TP53 wild-type
Relapsed to prior JAKi: progressive from BL or after a response-increased splenomegaly
Refractory to prior JAKi: lack of spleen response after ≥3 mo
SVR35 at 24 wk
Parsaclisib (PARS)
PI3Kδ inhibitor
LIMBER-304
NCT04551053
PARS + RUX vs PBO + RUX (estimated n = 212)
PARS 5 mg QD, RUX on the ongoing 2-mo stable dose
DIPSS Int/high-risk symptomatic MF
PLT ≥50 × 109/L
Spleen length ≥5 cm below LCM
≥3 mo of RUX, at stable dose for ≥2 mo
Suboptimal response to RUX: spleen of ≥5 cm below LCM and active symptoms at the screening visit
SVR35 at 24 wk
Luspatercept (LUS)
Activin receptor ligand trap
INDEPENDENCE
NCT04717414
LUS vs PBO in ongoing JAKi (estimated n = 309)
LUS 1.33 mg/kg q21
RBC-TD
DIPSS Int/high-risk MF
PLT as approved for the concomitant JAKi, neither <25 × 109/L nor ≥1000 × 109/L
JAKi for ≥8 mo with stable dose for ≥4 mo, and requirement of 4-12 RBC units/12 wk up to randomization RBC-TI ≥12 wk up to wk 24

BAT, best available therapy; BID, twice daily; BL, baseline; DIPSS: Dynamic International Prognostic Scoring System; JAKi, JAK inhibitor; LCM, left costal margin; MF, myelofibrosis; MTD, maximum tolerated doses; OS, overall survival; PBO, placebo; PLT, platelets; QD, once daily; RBC, red blood cells; RUX, ruxolitinib; SVR35, spleen volume reduction of 35%; TD, transfusion-dependence; TI, transfusion-independence.