Advanced solid tumors, neoplasms |
(14C)-Pevonedistat |
cumulative excretion of radioactive Pevonedistat in urine and feces/Circulatory and excretory pevonedistat metabolites
Report of TEAEs and SAEs
|
I |
NCT03057366 |
Recurrent AML, therapy-induced AML, untreated or recurrent AML |
Pevonedistat plus Decitabine |
Safety and tolerability of Pevonedistat added to Decitabine
MTD of pevonedistat in combination to Decitabine
mIR-155 expression, promoter methylation, and mIR-155 target gene expression (SHIP1/PU.1)
NF-kappaB expression and enrichment on mIR-155 promoter
|
I |
NCT03009240 |
Metastatic melanoma |
Pevonedistat |
MTD of 209 mg/m2
Clinical activity: 3% PR, 48% SD
Pevonedistat plasma concentration increased approximately proportionally with dose from 50 to 278 mg/m2 after Day 1 intravenous infusion
|
I |
NCT01011530 (*) (Bhatia et al., 2016) |
Solid tumors |
MLN4924 plus Docetaxel
2.]MLN4924 plus Docetaxel plus Carboplatin
MLN4924 plus Gemcitabine
|
Number of adverse events
Time course MLN4924 plasma concentration
|
I |
NCT01862328 |
Advanced solid tumors |
MLN4924 (schedules A and C) MLN4924 + Dexamethasone (Schedule B) |
MTD of 50 mg/m2 (schedule A) 50 and 67 mg/m2 (schedule B and C, respectively)
11/13 patients with > 20% increase in CDT1 and NRF2 CRLs substrates
13/14 patients show NEDD8 adducts in tumor biopsies
Clinical activity: 74% SD for schedules B and C
|
I |
NCT00677170 (*) (Sarantopoulos et al., 2016) |
AML |
MLN4924 plus Azacitidine |
Safety and tolerability of MLN4924 in combination with Azacitidine
Disease response rate
30-day and 60-day mortality rate
|
I |
NCT01814826 |
Advanced solid tumors |
MLN4924 Fluconazole Itraconazole Docetaxel Carboplatin Paclitaxel |
TEAEs and disease response
MLN4924 plasma concentration, blood to plasma ratio. MLN4924 clearance
Clinical response
|
I |
NCT02122770 |
AML, ALL, MDS |
MLN4924 Intravenous infusion on days 1, 3, and 5 (schedule A) and 1, 4, 8, and 11 (schedule B) |
MTD of 59 (Schedule A) and 83 mg/m2 (Schedule B)
Clinical activity: 17% CR/PR (schedule A); 10% CR/PR (schedule B)
32/35 patients with NEDD8 adduct in tumor biopsies
Pevonedistat increased within 4–8 h after infusion and returned to baseline within 24 h
|
I |
NCT00911066 (*) (Swords et al., 2015) |
Leukemia, MDS, Myeloid, Acute |
Pevonedistat
Pevonedistat plus Azacitidine
|
TEAEs and dose limiting toxicities
Overall and complete responses
Pevonedistat plasma concentration and clearance
|
I |
NCT02782468 |
Relapsed/refractory multiple Myeloma or lymphoma |
MLN4924 Intravenous infusion on Week 1, 2, 8, and 9 (schedule A) and 1, 4, 8, and 11 (schedule B) |
MTD of 110 mg/m2 (schedule A) and 196 mg/m2 (schedule B)
11/13 patients with NEDD8 adducts in bone marrow aspirates
CDT1 and NRF2 skin and NRF2 mRNA in blood increased in treated patients
Clinical activity: 1 patient with PR and 71% SD
|
I |
NCT00722488 (*) (Shah et al., 2016) |
Multiple myeloma Non-Hodgkin lymphoma |
TAS4464 |
Investigate the safety and tolerability of TAS4464; identify TAS4464 MTD
Efficacy of TAS4464, defined as Objective Response Rate (ORR) per IWG criteria (NHL) and IMWG criteria (MM).
|
I II |
NCT02978235 |
MDS leukemia, CML |
Azacitidine
Azacitidine plus Pevonedistat
|
EVF
OS
|
II |
NCT02610777 |
Non-small cell lung cancer |
Pevonedistat plus Docetaxel |
Response to treatment
Median progression free survival time, OS time, and patients who achieve stable disease
Toxicities by system organ class
|
II |
NCT03228186 |
MDS leukemia, CML, AML |
Azacytidine
Azacytidine plus Pevonedistat
|
EVF, OS, partial remission
overall response. 6 months and 1 year survival rate
|
II |
NCT02610777 |
MDS leukemia, CML |
Azacitidine
Azacitidine plus Pevonedistat
|
Overall response and EVF
OS
Pevonedistat plasma concentration
EVF and OS in participants with TP53 mutations or any adverse cytogenetic risk group
|
III |
NCT03268954 |