Phase 1
Completed N=23
A Study of Pevonedistat in Adult East Asian Participants
Leukemia, Myeloid, Acute · Myelodysplastic Syndromes
Source: ClinicalTrials.gov NCT02782468 ↗
Enrolled (actual)
23
Serious AEs
78.3%
Results posted
Nov 2023
Primary outcomePrimary: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) — 3; 7; 3; 10 Participants
Summary
The purpose of this study is to evaluate the safety and tolerability of pevonedistat administered as a single agent and in combination with azacitidine in adult east Asian participants with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
3; 7; 3; 10; 2; 7 | — |
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 During Cycle 1 |
0; 0; 0; 1 | — |
| PRIMARY Number of Participants With Clinically Significant Abnormal Laboratory Values |
0; 0; 0; 0 | — |
| PRIMARY Cmax: Maximum Observed Plasma Concentration for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 1 |
253; 410; 67.0; 160 | — |
| PRIMARY Cmax: Maximum Observed Plasma Concentration for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 5 |
252; 453; 76.1; 170 | — |
| PRIMARY AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 5 |
1515; 2163; 647; 1224 | — |
| PRIMARY CL: Total Clearance for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 1 |
24.1; 32.6; 22.8; 28.4 | — |
| PRIMARY CL: Total Clearance for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 5 |
24.0; 34.8; 28.1; 28.9 | — |
| SECONDARY Overall Response Rate (ORR) for Participants With AML |
0; 0; 50; 80 | — |
| SECONDARY ORR for Participants With MDS |
0; 100; 0 | — |
| SECONDARY Percentage of Participants With CR for Participants With AML |
0; 0; 50; 0 | — |
| SECONDARY Percentage of Participants With CR for Participants With MDS |
0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria include, in part:
- East Asian patients aged 18 years or older (or minimum age of legal consent consistent with local regulations) when written study informed consent is obtained must meet 1 of the following diagnosis criteria for either the Single-Agent Arm or the Combination Arm (additional restrictions apply to the Single Agent Arm):
a. Are male and female participants with WHO-defined AML, including leukemia secondary to prior chemotherapy or resulting from an antecedent hematologic disorder, who have failed to achieve CR or who have relapsed after prior therapy (R/R) and are not candidates for potentially curative treatment, or ii. Are male and female participants aged 60 years or older with previously untreated AML who have bone marrow blasts =5%
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Able to undergo bone marrow aspiration and biopsy at Screening.
Exclusion Criteria include, in part:
- Acute promyelocytic leukemia (as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics [t (15:17)] of peripheral blood or bone marrow, or by other accepted analysis) or AML associated with t (9;22) karyotypes or molecular.
- More than 3 prior lines of therapy (Combination Arm only).
- Prior therapy with hypomethylating agents (example, azacitidine, decitabine). (Combination Arm only).
- Is eligible for a hematopoietic stem cell transplant.
- Is a female participant who is lactating and breastfeeding or who have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
- Had treatment with any investigational products within 14 days before the first dose of any study drug.
- Has known hypersensitivity to azacitidine or mannitol (Combination Arm only).
- Has known central nervous system involvement.
- Had systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of any study drug, except for hydroxyurea.
Data sourced from ClinicalTrials.gov (NCT02782468). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.