Ongoing phase 3 trials in myelofibrosis
| Agent . | Class of investigational agent . | Trial . | n . | Phase 2 clinical benefit . | Primary outcome . | Key Secondary outcomes . | Comparator . | Population/key inclusion criteria . |
|---|---|---|---|---|---|---|---|---|
| JAKi-naive patients | ||||||||
| Pelabresib + ruxolitinib | BET inhibitor | MANIFEST-2 | 310 | Spleen reduction Less anemia BM fibrosis reduction | SVR ≥35% at 24 weeks | TSS at 24 weeks | Placebo + ruxolitinib | |
| Navitoclax + ruxolitinib | BCL2 inhibitor | TRANSFORM-1 | 230 | Spleen reduction | SVR ≥35% at 24 weeks | TSS at 24 weeks OS Reduction in BM fibrosis | Placebo + ruxolitinib | |
| Parsaclisib + ruxolitinib | PI3Kδ inhibitor | LIMBER-313 | 440 | Spleen reduction | SVR ≥35% at 24 weeks | TSS OS | Placebo + ruxolitinib | |
| Luspatercept + JAKi | ActRII ligand trap | INDEPENDENCE | 309 | Transfusion independence/anemia improvement | RBC transfusion independence at 24 weeks | Anemia improvement Duration of benefit | Placebo + JAKi | Transfusion dependent |
| Pacritinib | JAKi | PACIFICA | 348 | Spleen reduction Better tolerability in thrombocytopenic patients | SVR ≥35% at 24 weeks | TSS OS | Randomized 2:1 Physician selected BAT | Platelets <50 000/µL Includes patients with prior JAKi exposure |
| Jaktinib | JAKi | — | 105 | SVR ≥35% at 24 weeks | Transfusion dependence | Hydroxyurea | ||
| Following first-line JAKi exposure or failure | ||||||||
| Momelotinib | JAKi | MOMENTUM | 180 | Anemia improvement | TSS at 24 weeks | Transfusion independence Spleen response rate | Randomized 2:1 Danazol | Patients with anemia <100 g/L |
| Fedratinib | JAKi | FREEDOM-2 | 192 | Spleen reduction | SVR ≥35% at 24 weeks | TSS OS | Randomized 2:1 BAT | |
| Navitoclax + ruxolitinib | BCL2 inhibitor | TRANSFORM-2 | 330 | Spleen reduction | SVR ≥35% at 24 weeks | TSS at 24 weeks OS Reduction in BM fibrosis | BAT | |
| Parsaclisib + ruxolitinib | PI3Kδ inhibitor | LIMBER-304 | 212 | Spleen reduction | SVR ≥35% 24 weeks | TSS OS | Placebo + ruxolitinib | |
| Imetelstat | Telomerase inhibitor | IMpactMF | 320 | Symptom score reduction OS | OS | TSS at 24 weeks PFS SVR ≥35% at 24 weeks Reduction in BM fibrosis | BAT | |
| Agent . | Class of investigational agent . | Trial . | n . | Phase 2 clinical benefit . | Primary outcome . | Key Secondary outcomes . | Comparator . | Population/key inclusion criteria . |
|---|---|---|---|---|---|---|---|---|
| JAKi-naive patients | ||||||||
| Pelabresib + ruxolitinib | BET inhibitor | MANIFEST-2 | 310 | Spleen reduction Less anemia BM fibrosis reduction | SVR ≥35% at 24 weeks | TSS at 24 weeks | Placebo + ruxolitinib | |
| Navitoclax + ruxolitinib | BCL2 inhibitor | TRANSFORM-1 | 230 | Spleen reduction | SVR ≥35% at 24 weeks | TSS at 24 weeks OS Reduction in BM fibrosis | Placebo + ruxolitinib | |
| Parsaclisib + ruxolitinib | PI3Kδ inhibitor | LIMBER-313 | 440 | Spleen reduction | SVR ≥35% at 24 weeks | TSS OS | Placebo + ruxolitinib | |
| Luspatercept + JAKi | ActRII ligand trap | INDEPENDENCE | 309 | Transfusion independence/anemia improvement | RBC transfusion independence at 24 weeks | Anemia improvement Duration of benefit | Placebo + JAKi | Transfusion dependent |
| Pacritinib | JAKi | PACIFICA | 348 | Spleen reduction Better tolerability in thrombocytopenic patients | SVR ≥35% at 24 weeks | TSS OS | Randomized 2:1 Physician selected BAT | Platelets <50 000/µL Includes patients with prior JAKi exposure |
| Jaktinib | JAKi | — | 105 | SVR ≥35% at 24 weeks | Transfusion dependence | Hydroxyurea | ||
| Following first-line JAKi exposure or failure | ||||||||
| Momelotinib | JAKi | MOMENTUM | 180 | Anemia improvement | TSS at 24 weeks | Transfusion independence Spleen response rate | Randomized 2:1 Danazol | Patients with anemia <100 g/L |
| Fedratinib | JAKi | FREEDOM-2 | 192 | Spleen reduction | SVR ≥35% at 24 weeks | TSS OS | Randomized 2:1 BAT | |
| Navitoclax + ruxolitinib | BCL2 inhibitor | TRANSFORM-2 | 330 | Spleen reduction | SVR ≥35% at 24 weeks | TSS at 24 weeks OS Reduction in BM fibrosis | BAT | |
| Parsaclisib + ruxolitinib | PI3Kδ inhibitor | LIMBER-304 | 212 | Spleen reduction | SVR ≥35% 24 weeks | TSS OS | Placebo + ruxolitinib | |
| Imetelstat | Telomerase inhibitor | IMpactMF | 320 | Symptom score reduction OS | OS | TSS at 24 weeks PFS SVR ≥35% at 24 weeks Reduction in BM fibrosis | BAT | |
BAT, best available therapy; BCL2, B-cell lymphoma 2; BET, bromodomain and extraterminal; PFS, progression-free survival; SVR, spleen volume response; TSS, total symptom score.
Source: https://www.clinicaltrials.gov accessed on April 30, 2021.