Table 2.
Agents currently in early phase of clinical development in myelofibrosis
| Drug | Mechanism of action | Setting | End points | Status | NCT id | References |
|---|---|---|---|---|---|---|
| PIM447 and LEE011 | pan-PIM inhibitor, and CDK4/6 inhibitor | Add on to ruxolitinib phase 1b | Incidence of DLTs | A | NCT02370706 | [93] |
| Enasidenib | IDH2 inhibitor | Add on phase 2 | 20—Proportion of patients with any response* | NYR | NCT04281498 | [94] |
| APG-1252 | parenteral BH3 mimetic | Add on phase 1b/2 | DLT at each dose level; SVR35% or TSS50 | NYR | NCT04354727 | – |
| PU-H71 | Epichaperome-specific Hsp90 inhibitor | Add on phase 1b | – | Terminated as of 10/22/20 | NCT03373877 | [95] |
| 1. Siremadlin | 1. Inhibits p53-MDM2 interaction | Add on phase 1 parallel design | Incidence DLT within the first 2 cycles; response at the end of 6 cycles—composite of anemia improvement and no spleen volume progression and no symptom worsening | R | NCT04097821 (ADORE trial—platform design) | – |
| 2. Crizanlizumab | 2. P-selectin monoclonal antibody | |||||
| 3. MBG453 | 3. humanized anti-TIM-3 IgG4 antibody | |||||
| 9-ING-41 | Glycogen Synthase Kinase-3β inhibitor | Add on phase 2 | % of patients with response according to the Revised IWG-MRT and ELN Response Criteria for MF (2013) | R | NCT04218071 | [96] |
| Selinexor | nuclear-cytoplasmic transport inhibitor | Second line | Change in spleen volume within 6 months | R | NCT03627403 | [97] |
| Pevonedistat | NEDD8 activating enzyme inhibitor | Add on | Safety and tolerability of the combination as measured by the incidence of AEs and MTD | R | NCT03386214 | [98] |
| Pembrolizumab Nivolumab | PD-1 pathway inhibitors | Second line | Response per ELN-IWG criteria | Completed Terminate | NCT03065400 | [99] |
| NCT02421354 | ||||||
| AVID200 | Selective TGFβ1 ligand trap | Second line Phase 1 | MTD and number of patients with response eligibility for Phase 1b | R | NCT03895112 | [100] |
| ONC201 | p53 independent promoter of apoptosis | Second-line phase 1 | – | – | TBD | [101] |
| TP3654 | second-generation pan-PIM kinase inhibitor | Second-line phase 1 | Determine the incidence of DLT and AE | R | NCT04176198 | [102] |
PIM-Proviral Integration Site for Moloney Murine Leukemia Virus; CDK—Cyclin-Dependent Kinase; IDH—isocitrate dehydrogenase; BH3—B-cell lymphoma 2 (Bcl-2) homology 3; Hsp—heat-shock protein; MDM—murine double minute; TIM—T-cell immunoglobulin and mucin domain; NEDD—Neural precursor cell-Expressed Developmentally Downregulated genes; PD—programmed cell death protein; TGF-transforming growth factor; DLT-dose-limiting toxicity; A-active; NYR—not yet recruiting; R-recruiting; *—in MF pts; SVR35%-35% reduction in spleen volume within 24 weeks; TSS50- ≥ 50% reduction in myelofibrosis-related total symptom score within 24 weeks; AE—adverse events; MTD—maximum tolerated dose