trialsTrialCompleted

Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)

A phase 3 trial of Azacitidine and Pevonedistat in Leukaemia, run by Takeda, completed.

Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML) is a phase 3 interventional study registered as NCT03268954 by Takeda, with 454 participants recorded, started 2017-11-28 and reaching its primary completion in 2021-05-28. Interventions recorded: Azacitidine, Pevonedistat. Conditions recorded: Myelodysplastic Syndrome, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute.

Linked to the drug Pevonedistat because the registry names it among its interventions and Leukaemia among its conditions. Registry record only: no result has been read by an editor.

Setting

A Phase 3, Randomized, Controlled, Open-label, Clinical Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Patients With Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Low-Blast Acute Myelogenous Leukemia

Phase

Phase 3

Sponsor

Takeda

Registry

NCT03268954

Started

2017-11-28

Reported

2022

Enrolled

454 enrolled

Outcomes

2top

In plain words

What these results mean for people, not percentages

454 enrolled

Event-Free Survival (EFS)primarysurrogate endpoint

Median 15.7 vs 17.7 months with Azacitidine 75 mg/m^2 compared with Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2; about 2 months shorter for half the group.
A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
Put another way, the treated group had about 3 percent lower chance of the event at any given time (hazard ratio 0.968, likely range 0.757 to 1.238).

This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.

Overall Survival (OS)survival endpoint

Median 16.8 vs 20.3 months with Azacitidine 75 mg/m^2 compared with Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2; about 3.5 months shorter for half the group.
A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
Put another way, the treated group had about 11 percent lower chance of the event at any given time (hazard ratio 0.888, likely range 0.709 to 1.113).

Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.

Caveats

The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
These results apply to the people the trial enrolled: A Phase 3, Randomized, Controlled, Open-label, Clinical Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Patients With Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Low-Blast Acute Myelogenous Leukemia. People in a different situation may not see the same effect.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

454 enrolled.

Event-Free Survival (EFS)primary

HR 0.968 (0.757 to 1.238) · p = 0.557

Download

95% CI 14.42 to 19.68; Figures from the ClinicalTrials.gov results section (first posted 2022-09-22), not from a publication · 95% CI 13.63 to 20.24

Source

Overall Survival (OS)

HR 0.888 (0.709 to 1.113) · p = 0.152

Download

95% CI 14.92 to 20.11; Figures from the ClinicalTrials.gov results section (first posted 2022-09-22), not from a publication · 95% CI 17.97 to 22.60

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Event-Free Survival (EFS)primary	Azacitidine 75 mg/m^2	227	15.7 months	0.968 (0.757 to 1.238)	0.557	link
Event-Free Survival (EFS)primary	Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2	227	17.7 months	0.968 (0.757 to 1.238)	0.557	link
Overall Survival (OS)	Azacitidine 75 mg/m^2	227	16.8 months	0.888 (0.709 to 1.113)	0.152	link
Overall Survival (OS)	Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2	227	20.3 months	0.888 (0.709 to 1.113)	0.152	link

Connected

4top

Trial
Study to Compare Azacitidine Plus Pevonedistat Versus Azacitidine in Patients With Acute Myeloid Leukemia Not Eligible for Standard Chemotherapy
Shares Pevonedistat, Azacitidine, Leukaemia (all types) and the tag pipeline.
Trial
Continuation Study of B1371019(NCT03416179) and B1371012(NCT02367456) Evaluating Azacitidine With Or Without Glasdegib In Patients With Previously Untreated AML, MDS or CMML
Shares Azacitidine, Leukaemia (all types) and the tag pipeline.
Trial
A Study of TAK-007 in Adults With Relapsed or Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL)
Shares Takeda and the tag pipeline.
Trial
A Study of Gammagard Liquid (Immune Globulin Infusion, 10%) to Prevent Infections in Adults With Multiple Myeloma
Shares Takeda and the tag pipeline.
Trial
A Study of TAK-188 in Adults With Advanced or Spreading Solid Tumors
Shares Takeda and the tag pipeline.
Trial
A Study of TAK-505 in Adults With Solid Tumors
Shares Takeda and the tag pipeline.
Trial
A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia
Shares Azacitidine, Leukaemia (all types) and the tag pipeline.
Trial
Study of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients
Shares Azacitidine, Leukaemia (all types) and the tag pipeline.

cancers

Leukaemia (all types)

drugs

ApprovedSmall-molecule hypomethylating agent (cytotoxic)

Azacitidine · Vidaza / Onureg (oral)

NegativeIntravenous NEDD8-activating enzyme (NAE) inhibitor

Pevonedistat

companies

Takeda

Evidence strength62/100 · Solid

How much and what kind of evidence, not how big the benefit. Click for the breakdown.

Phase 3+30
454 enrolled+13
Primary endpoint: time to progression or recurrence+14
Result: completed0
No independent replication recorded0
A linked product is approved+5

Formula disclosed on the evidence page.

ProvenanceLast edited 2026-09-22 · Jude Gomila · Wave 5 drugs · diff · file

Sources & links

ClinicalTrials.gov NCT03268954

Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)

A phase 3 trial of Azacitidine and Pevonedistat in Leukaemia, run by Takeda, completed.

Linked to the drug Pevonedistat because the registry names it among its interventions and Leukaemia among its conditions. Registry record only: no result has been read by an editor.

Setting

Phase

Phase 3

Sponsor

Takeda

Registry

NCT03268954

Started

2017-11-28

Reported

2022

Enrolled

454 enrolled

Outcomes

2top

In plain words

What these results mean for people, not percentages

454 enrolled

Event-Free Survival (EFS)primarysurrogate endpoint

Median 15.7 vs 17.7 months with Azacitidine 75 mg/m^2 compared with Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2; about 2 months shorter for half the group.
A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
Put another way, the treated group had about 3 percent lower chance of the event at any given time (hazard ratio 0.968, likely range 0.757 to 1.238).

This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.

Overall Survival (OS)survival endpoint

Median 16.8 vs 20.3 months with Azacitidine 75 mg/m^2 compared with Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2; about 3.5 months shorter for half the group.
A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
Put another way, the treated group had about 11 percent lower chance of the event at any given time (hazard ratio 0.888, likely range 0.709 to 1.113).

Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.

Caveats

The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
These results apply to the people the trial enrolled: A Phase 3, Randomized, Controlled, Open-label, Clinical Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Patients With Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Low-Blast Acute Myelogenous Leukemia. People in a different situation may not see the same effect.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

454 enrolled.

Event-Free Survival (EFS)primary

HR 0.968 (0.757 to 1.238) · p = 0.557

Download

95% CI 14.42 to 19.68; Figures from the ClinicalTrials.gov results section (first posted 2022-09-22), not from a publication · 95% CI 13.63 to 20.24

Source

Overall Survival (OS)

HR 0.888 (0.709 to 1.113) · p = 0.152

Download

95% CI 14.92 to 20.11; Figures from the ClinicalTrials.gov results section (first posted 2022-09-22), not from a publication · 95% CI 17.97 to 22.60

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Event-Free Survival (EFS)primary	Azacitidine 75 mg/m^2	227	15.7 months	0.968 (0.757 to 1.238)	0.557	link
Event-Free Survival (EFS)primary	Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2	227	17.7 months	0.968 (0.757 to 1.238)	0.557	link
Overall Survival (OS)	Azacitidine 75 mg/m^2	227	16.8 months	0.888 (0.709 to 1.113)	0.152	link
Overall Survival (OS)	Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2	227	20.3 months	0.888 (0.709 to 1.113)	0.152	link

Connected

4top

Trial
Study to Compare Azacitidine Plus Pevonedistat Versus Azacitidine in Patients With Acute Myeloid Leukemia Not Eligible for Standard Chemotherapy
Shares Pevonedistat, Azacitidine, Leukaemia (all types) and the tag pipeline.
Trial
Continuation Study of B1371019(NCT03416179) and B1371012(NCT02367456) Evaluating Azacitidine With Or Without Glasdegib In Patients With Previously Untreated AML, MDS or CMML
Shares Azacitidine, Leukaemia (all types) and the tag pipeline.
Trial
A Study of TAK-007 in Adults With Relapsed or Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL)
Shares Takeda and the tag pipeline.
Trial
A Study of Gammagard Liquid (Immune Globulin Infusion, 10%) to Prevent Infections in Adults With Multiple Myeloma
Shares Takeda and the tag pipeline.
Trial
A Study of TAK-188 in Adults With Advanced or Spreading Solid Tumors
Shares Takeda and the tag pipeline.
Trial
A Study of TAK-505 in Adults With Solid Tumors
Shares Takeda and the tag pipeline.
Trial
A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia
Shares Azacitidine, Leukaemia (all types) and the tag pipeline.
Trial
Study of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients
Shares Azacitidine, Leukaemia (all types) and the tag pipeline.

cancers

Leukaemia (all types)

drugs

ApprovedSmall-molecule hypomethylating agent (cytotoxic)

Azacitidine · Vidaza / Onureg (oral)

NegativeIntravenous NEDD8-activating enzyme (NAE) inhibitor

Pevonedistat

companies

Takeda

Evidence strength62/100 · Solid

How much and what kind of evidence, not how big the benefit. Click for the breakdown.

Phase 3+30
454 enrolled+13
Primary endpoint: time to progression or recurrence+14
Result: completed0
No independent replication recorded0
A linked product is approved+5

Formula disclosed on the evidence page.

ProvenanceLast edited 2026-09-22 · Jude Gomila · Wave 5 drugs · diff · file

Sources & links

ClinicalTrials.gov NCT03268954

Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)

Outcomes

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Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)

Outcomes

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Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)

Overview

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Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)

Overview

Outcomes

Connected

Similar pages

cancers

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companies