Drugs / Pevonedistat
last change Jul 2026 re-read 9 days ago

Pevonedistat

Small molecule targets MCL1 via inhibition

Developed for
acute myeloid leukemia · myelodysplastic syndrome · chronic myelomonocytic leukemia · high grade malignant neoplasm · acute lymphoblastic leukemia · diffuse large B-cell lymphoma · myelofibrosis · plasma cell myeloma
+21 more · therapy related acute myeloid leukemia and myelodysplastic syndrome · acute myeloid leukemia with multilineage dysplasia · B-cell prolymphocytic leukemia · cancer · cancer or benign tumor · central nervous system neoplasm · chronic lymphocytic leukemia/small lymphocytic lymphoma · follicular lymphoma · Hodgkins lymphoma · intrahepatic cholangiocarcinoma · lymphoma · lymphoplasmacytic lymphoma · mantle cell lymphoma · marginal zone lymphoma · mesothelioma · metastatic malignant neoplasm · metastatic melanoma · myeloproliferative neoplasm · non-small cell lung carcinoma · non-small cell squamous lung carcinoma · Richter transformation
Investigated by
Millennium Pharmaceuticals, Inc. · National Cancer Institute (NCI) · Takeda · M.D. Anderson Cancer Center · Children's Oncology Group · City of Hope Medical Center
+17 more · AVEO Pharmaceuticals, Inc. · Beat AML, LLC · Dynamic Science S.L. · HOVON Foundation · Justin Watts, MD · Medical College of Wisconsin · Memorial Sloan Kettering Cancer Center · Milton S. Hershey Medical Center · PETHEMA Foundation · Syndax Pharmaceuticals · Takeda Development Center Americas, Inc. · University of Leipzig · University of Miami · University of Michigan Rogel Cancer Center · University of Southern California · Vanderbilt-Ingram Cancer Center · Washington University School of Medicine

Trials 41

PhaseRegistry idDatesIndicationSponsorStatusOutcome
Phase 122 trials
Phase 1 NCT03770260 Feb 2020 → Sep 2022 plasma cell myeloma National Cancer Institute (NCI) Completed No outcome recorded
Phase 1 NCT04172844 Jan 2020 → Dec 2021 acute myeloid leukemia Medical College of Wisconsin Terminated No outcome recorded
Phase 1 NCT03814005 Jul 2019 → Mar 2021 acute myeloid leukemia, chronic myelomonocytic leukemia, impaired renal function disease, liver disorder +1 Takeda Completed No outcome recorded
Phase 1 NCT03772925 Jun 2019 → Sep 2022 acute myeloid leukemia, myelodysplastic syndrome National Cancer Institute (NCI) Terminated No outcome recorded
Phase 1 NCT03813147 May 2019 → Sep 2021 acute myeloid leukemia, myelodysplastic syndrome National Cancer Institute (NCI) Completed No outcome recorded
Phase 1 NCT03349281 Mar 2019 → Aug 2021 acute lymphoblastic leukemia University of Miami Completed No outcome recorded
Phase 1 NCT03486314 Aug 2018 → May 2019 high grade malignant neoplasm Millennium Pharmaceuticals, Inc. Completed No outcome recorded
Phase 1 NCT03459859 May 2018 → Jun 2021 acute myeloid leukemia, myelodysplastic syndrome Justin Watts, MD Completed No outcome recorded
Phase 1 NCT03479268 Apr 2018 → Nov 2026 expected B-cell prolymphocytic leukemia, Richter transformation, chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma +4 City of Hope Medical Center Active not recruiting No outcome recorded
Phase 1 NCT03386214 Apr 2018 → Sep 2021 myelofibrosis Washington University School of Medicine Terminated No outcome recorded
Phase 1/25 trials
Phase 1/2 NCT04800627 Mar 2021 → Nov 2022 high grade malignant neoplasm, metastatic malignant neoplasm M.D. Anderson Cancer Center Terminated No outcome recorded
Phase 1/2 NCT03862157 Feb 2019 → Jan 2027 expected acquired polycythemia vera, acute myeloid leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, chronic eosinophilic leukemia +7 M.D. Anderson Cancer Center Active not recruiting No outcome recorded
Phase 1/2 NCT03330821 Apr 2018 → Dec 2026 expected acute myeloid leukemia with multilineage dysplasia, therapy related acute myeloid leukemia and myelodysplastic syndrome University of Southern California Active not recruiting No outcome recorded
Phase 1/2 NCT03319537 Oct 2017 → Jun 2023 mesothelioma Memorial Sloan Kettering Cancer Center Terminated No outcome recorded
Phase 1/2 NCT01415765 Jul 2011 → Jan 2014 diffuse large B-cell lymphoma National Cancer Institute (NCI) Withdrawn No outcome recorded
Phase 210 trials · 2 missed
Phase 2 NCT04985656 Oct 2021 → Jan 2024 myelodysplastic syndrome Takeda Withdrawn No outcome recorded Stop: Business
Phase 2 NCT04712942 Jan 2021 → Jan 2023 acute myeloid leukemia, myelodysplastic syndrome University of Leipzig Completed No outcome recorded
Phase 2 NCT04266795 Oct 2020 → Sep 2022 acute myeloid leukemia Takeda Completed Missed primary
Phase 2 NCT03965689 Apr 2020 → Sep 2022 overdue non-small cell squamous lung carcinoma National Cancer Institute (NCI) Active not recruiting No outcome recorded
Phase 2 NCT04175912 Mar 2020 → Nov 2023 overdue hepatocellular carcinoma, intrahepatic cholangiocarcinoma National Cancer Institute (NCI) Active not recruiting No outcome recorded
Phase 2 NCT03745352 May 2019 → Aug 2021 acute myeloid leukemia National Cancer Institute (NCI) Withdrawn No outcome recorded Stop: Enrollment
Phase 2 NCT03709576 Jul 2018 → Jul 2019 acute myeloid leukemia Milton S. Hershey Medical Center Terminated No outcome recorded Stop: Business
Phase 2 NCT03228186 Mar 2018 → Nov 2021 non-small cell lung carcinoma University of Michigan Rogel Cancer Center Terminated No outcome recorded
Phase 2 NCT03238248 Aug 2017 → Sep 2022 myelodysplastic syndrome, myeloproliferative neoplasm Vanderbilt-Ingram Cancer Center Completed No outcome recorded
Phase 2 NCT02610777 Apr 2016 → Sep 2019 acute myeloid leukemia, chronic myelomonocytic leukemia, myelodysplastic syndrome Millennium Pharmaceuticals, Inc. Completed Missed primary
Phase 2/31 trial
Phase 2/3 NCT03013998 Nov 2016 → Dec 2032 expected acute myeloid leukemia Beat AML, LLC Recruiting No outcome recorded
Phase 32 trials · 1 missed
Phase 3 NCT04090736 Sep 2019 → Jun 2023 overdue acute myeloid leukemia PETHEMA Foundation Active not recruiting No outcome recorded
Phase 3 NCT03268954 Nov 2017 → May 2021 acute myeloid leukemia, chronic myelomonocytic leukemia, myelodysplastic syndrome Takeda Completed Missed primary
Phase not stated1 trial
— NCT04484363 — myelodysplastic syndrome Takeda No longer available No outcome recorded

News releases announcing trial results or a regulatory action · 4

DateIssuerRelease
2021-09-01 Takeda Results Takeda Provides Update on Phase 3 PANTHER (Pevonedistat-3001) Trial takeda.com ↗
Takeda Pharmaceutical Company Limited ( TSE:4502/NYSE:TAK ) (“Takeda”) today announced that the Phase 3 PANTHER (Pevonedistat-3001) study did not achieve pre-defined statistical significance for the primary endpoint of event-free survival (EFS).
2020-11-05 Takeda Results Takeda Oncology Demonstrates Leadership in Hematologic Cancers at 62nd American Society of Hematology (ASH) Annual Meeting takeda.com ↗
2020-07-30 Takeda Regulatory Takeda Announces U.S. FDA Breakthrough Therapy Designation Granted for Pevonedistat for the Treatment of Patients with Higher-Risk Myelodysplastic Syndromes (HR-MDS) takeda.com ↗
Takeda Pharmaceutical Company Limited ( TSE:4502/NYSE:TAK ) today announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for its investigational drug pevonedistat for the treatment of patients with higher-risk myelodysplastic syndromes (HR-MDS).
2020-05-29 Takeda Results Takeda Announces Compelling Data from the Phase 2 Trial of Pevonedistat Plus Azacitidine in Patients with Higher-Risk MDS takeda.com ↗
Pevonedistat Combination Demonstrates the Potential to Double Complete Remissions and Improve Outcomes in HR-MDS, With Safety Profile Similar to Azacitidine Alone

Evidence & citations 13 cited values

Every value below carries the sentence it was read from. 47 sources stand behind the page.

FieldValueCited text
Known as Pevonedistat “Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes” PMID 25733005 ↗ Mar 2015
34

“pevonedistat (also known as MLN4924) is the only NEDDylation inhibitor to date to enter phase III clinical trials.” PMID 41687727 ↗ Feb 2026

“Drug: Pevonedistat” NCT04172844 ↗

NCT04800627 ↗

NCT03772925 ↗

NCT03330106 ↗

NCT03965689 ↗

NCT04985656 ↗

NCT03013998 ↗

NCT03459859 ↗

NCT03238248 ↗

Show 24 more sources

Known as MLN-4924 HYDROCHLORIDE ChEMBL registry synonym — accepted as the source's own label CHEMBL1231160 ↗
Known as MLN-4924-003 ChEMBL registry synonym — accepted as the source's own label CHEMBL1231160 ↗
Known as MLN4924 “A Phase 1/1b, Open-label Study of Pevonedistat (MLN4924, TAK-924) as Single Agent and in Combination With Azacitidine in Adult East Asian Patients With Acute Myeloid Leukemia...” NCT02782468 ↗
10

“A Phase II Study of Pevonedistat (MLN4924, TAK924) and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission Acute Myelogenous Leukemia” NCT03709576 ↗

“Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme (NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia (AML).” PMID 29348128 ↗ Jan 2018

NCT00677170 ↗

NCT01011530 ↗

NCT00911066 ↗

NCT01814826 ↗

NCT01415765 ↗

NCT01862328 ↗

NCT00722488 ↗

NCT02122770 ↗

Known as PEVONEDISTAT (MLN4924) ChEMBL registry synonym — accepted as the source's own label CHEMBL1231160 ↗
Known as PEVONEDISTAT HYDROCHLORIDE ChEMBL registry synonym — accepted as the source's own label CHEMBL1231160 ↗
Known as TAK-924/MLN4924 “The drug being tested in this study is called Pevonedistat (TAK-924/MLN4924).” NCT04985656 ↗
Known as TAK924 “A Phase 1/1b, Open-label Study of Pevonedistat (MLN4924, TAK-924) as Single Agent and in Combination With Azacitidine in Adult East Asian Patients With Acute Myeloid Leukemia...” NCT02782468 ↗
2

“A Phase II Study of Pevonedistat (MLN4924, TAK924) and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission Acute Myelogenous Leukemia” NCT03709576 ↗

“Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme (NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia (AML).” PMID 29348128 ↗ Jan 2018

Known as UNII-S3AZD8D215 ChEMBL registry synonym — accepted as the source's own label CHEMBL1231160 ↗
Action Inhibit “a Novel Inhibitor of Nedd8-Activating Enzyme” NCT00677170 ↗
Modality Small molecule “Pevonedistat, the first small-molecule inhibitor of NEDD8-activating enzyme” PMID 35545778 ↗ May 2022
Route Intravenous “IV dose escalation for 5 consecutive days” NCT00677170 ↗
Target MCL1 “Pevonedistat inhibits MCL1 through activation of NOXA” PMID 38572562 ↗ Sep 2024