Skip to main content

Table 1 List of trials assessing the use of targeted therapy in high-risk myelodysplastic syndrome

From: Treatment of myelodysplastic syndromes in the era of precision medicine and immunomodulatory drugs: a focus on higher-risk disease

Drug

Mechanism of action and target

Combination

NCT

Patient population

Trial design

Outcomes

Status

References

Cedazuridine/decitabine

HMA with cytidine deaminase inhibitor

Monotherapy

NCT03306264

N = 133

MDS and CMML

Phase III

(ASCERTAIN)

PKs equivalence between oral and IV AUC 98.9%

ORR: 61.7%

CR: 22%

mOS: 31.7 m

LFS: 29.1 m

Completed

[27, 29]

Cedazuridine/decitabine

HMA with cytidine deaminase inhibitor

 + 

BCL2 inhibitor

Venetoclax

NCT04655755

N = 9

HR-MDS and CMML

Phase I

ORR: 100%

CR: 67% with venetoclax 200 mg and 17% with venetoclax 400 mg

Ongoing

[30]

Azacitidine

HMA

 + 

BCL2 inhibitor

Venetoclax

NCT02942290

N = 51 receiving RP2D

Untreated HR-MDS

Phase Ib

ORR: 84%

CR: 40%

mDoR: 13 m

Time to CR: 2.6 m

mOS in pts with CR: 28.6 m

Ongoing

[39]

NCT04401748

N = 500

Untreated HR-MDS

Phase III

VERONA

No results yet

Ongoing

[40]

NCT02966782

N = 37

R/R HR-MDS

Phase Ib

ORR: 39%

CR: 7%

mDoR: 8.6 m

mOS: 14.8 m

Ongoing

[42]

APR-246

TP53 inhibitor

Azacitidine

NCT03072043

N = 40

MDS with at least one TP53 mutation

Phase II

ORR: 73%

CR: 50%

Completed

[46]

Azacitidine with or without APR-246

NCT03745716

N = 154

TP53-mutated MDS

Phase III

CR: 34.6% (APR-246) vs 22.4% (no APR-246)

Completed

[48]

Pevonedistat

Inhibitor of the NEDD8-activating enzyme

With or without azacitidine

NCT02610777

N = 120

HR-MDS, HR-CMML, and low-blasts AML

Phase II

ORR: 79% (comb) vs 57%, p = 0.065

CR: 52% (comb) vs 27%, p = 0.050

Completed

[53]

NCT03268954

N = 454

HR-MDS, CMML, and low-blasts AML

Phase III

(PANTHER)

CR: 24% (comb) vs 32%

EFS: 17.7 (comb) vs 15.7 m, p = 0.557

Completed

[54]

Ivosidenib

IDH1 inhibitor

Monotherapy

NCT02074839

Patients with hematologic malignancies

N = 12 with R/R MDS

Phase I

ORR: 75%

mDoR: 21.4 m

Ongoing

[55]

NCT03503409

N = 26

(A): failed HMA

(B): untreated

(C): low-risk MDS

Phase II

IDIOME

ORR = 69% (A: 54%, B: 91%)

CR = 46% (A: 23%: B: 73%)

mDoR = 7.4 m

mOS = 14 m (A: 7.7 m; B: not reached)

Ongoing

[56]

Enasidenib

IDH2 inhibitor

Monotherapy

NCT01915498

Patients with hematologic malignancies

N = 17 with MDS

Phase I/II

Prior MDS treatment:

ORR = 46%

No prior MDS treatment:

ORR = 75% (3/4)

mDoR = 9 m

mEFS: 11 m

mOS: 16.9 m

Ongoing, close for recruitment

[57]

With or without azacitidine

NCT03383575

N = 21, R/R MDS

N = 25, untreated MDS

Phase II

ORR: 84% (comb) vs 43%

CR: 24% both arms

mOS 32.2 m (comb) vs 21.3 m

Ongoing

[58]

Emavusertib

CA-4948

IRAK4 inhibitor

With azacitidine

NCT04278768

N = 43

R/R AML and HR-MDS

Phase I/IIa

Patients with MDS and SF3B1/U2AF1/FLT3 mutations:

CR: 57%

All patients without SF3B1/U2AF1/FLT3 mutations:

CR: 1/29 (3.5%)

Ongoing

[72, 73]

  1. HMA: hypomethylating agents; MDS: myelodysplastic syndrome; PKs: pharmacokinetics; AUC: area under the curve; ORR: overall response rate; CR: complete response; mOS: median overall survival; LFS: leukemia-free survival; HR: high risk; CMML: chronic myelomonocytic leukemia; mDoR: median duration of response; AML: acute myeloid leukemia; comb: combination; and EFS: event-free survival; m: months