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Table 2 Agents currently in early phase of clinical development in myelofibrosis

From: Novel therapeutics in myeloproliferative neoplasms

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]
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]
  1. 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