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

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]