01.12.2017 | Review | Ausgabe 1/2017 Open Access

MDM2/X inhibitors under clinical evaluation: perspectives for the management of hematological malignancies and pediatric cancer
- Zeitschrift:
- Journal of Hematology & Oncology > Ausgabe 1/2017
Background
The MDM2/X genes and proteins
Disease
|
TP53 mutations
|
TP53 17p deletion
|
MDM2 overexpression/trisomy 12
|
MDMX overexpression
|
References
|
---|---|---|---|---|---|
ALL
|
13.5 ± 0.7 (459 pt)
|
4.3 ± 1.2 (1731 pt)
|
29.3 ± 4.7 (101 pt)
|
80 (55 pt)
|
|
AML
|
13.5 ± 2.7 (2934 pt)
|
1.5 ± 0.7 (2398 pt)
|
49 (189 pt)
|
10.7 (140 pt)
|
|
BL
|
17.3 ± 9 (218 pt)
|
10 (28 pt)
|
13.5 ± 13.4 (109 pt)
|
21 (30 pt)
|
|
CLL
|
10.2 ± 1.5 (3703 pt)
|
6.8 ± 1.9 (3523 pt)
|
13.8 ± 1.8 (3523 pt)
|
21 (131 pt)
|
|
MM
|
8.2 ± 5.2 (733 pt)
|
10.2 ± 2.7 (954 pt)
|
8 (82 pt)
|
na
|
|
NHL
|
24.4 ± 6.4 (1337 pt)
|
25 ± 7.1 (75 pt)
|
15.1 ± 17.2 (851 pt)
|
na
|
|
WM/LPL
|
7 (30 pt)
|
8.7 ± 1 (206 pt)
|
4 ± 1.4 (214 pt)
|
na
|
The MDM2/X axis with P53
Targeting the MDM2/X-P53 axis for therapeutic purposes
Compound
|
Clinical study
|
Phase
|
Status
|
Clinical trial identifier
|
---|---|---|---|---|
RG7112 RO5045337
|
Extension study to provide treatment to participants who have completed parent studies
|
1
|
Active, not recruiting
|
NCT01677780
|
Solid tumors
|
1
|
Completed
|
NCT01164033
|
|
Patients with liposarcoma who are eligible for debulking surgery
|
1
|
Completed
|
NCT01143740
|
|
Soft tissue sarcoma: treatment in combination with doxorubicin
|
1
|
Completed
|
NCT01605526
|
|
AML, ALL, CML in blast phase, refractory CLL/SCLL
|
1
|
Completed
|
NCT00623870
|
|
Advanced solid tumors including lymphoma
|
1
|
Completed
|
NCT00559533
|
|
AML: treatment combination with cytarabine
|
1
|
Completed
|
NCT01635296
|
|
RG7388 RO5503781
Idasanutlin
|
Essential thrombocythemia and polycythemia vera
|
1
|
Recruiting
|
NCT02407080
|
Solid tumors: determination of excretion balance, pharmacokinetics, metabolism and bioavailability
|
1
|
Active, not recruiting
|
NCT02828930
|
|
Multiple myeloma: combinations with ixazomib citrate and dexamethasone
|
1/2
|
Recruiting
|
NCT02633059
|
|
R/R AML: combination with cytarabine
|
3
|
Recruiting
|
NCT02545283
|
|
In R/R FL in combination with obinutuzumab and in DLBCL combination with rituximab
|
1b/2
|
Recruiting
|
NCT02624986
|
|
R/R AML patients not eligible for cytotoxic therapy: combination with venetoclax
|
1/2
|
Recruiting
|
NCT02670044
|
|
Prostate cancer who haven’t had docetaxel: Idasanutlin with abiraterone or enzalutamide
|
1/2
|
Open
|
CRUKE/12/032
|
|
Solid tumors: effect of posaconazole on pharmacokinetics, bioavailability of new formulations
|
1
|
Completed
|
NCT01901172
|
|
AML: combination with cytarabine
|
1
|
Completed
|
NCT01773408
|
|
Advanced malignancies except leukemia
|
1
|
Completed
|
NCT01462175
|
|
SAR405838 MI-77301
|
Advanced cancer
|
1
|
Active not recruiting
|
NCT01636479
|
Advanced cancer (solid tumors): combination with pimasertib
|
1
|
Completed
|
NCT01985191
|
|
MK-8242 SCH 900242
|
Advanced solid tumors: study of safety and pharmacokinetics
|
1
|
Completed
|
NCT01463696
|
AML: alone and in combination with cytarabine
|
1
|
Completed
|
NCT01451437
|
|
AMG232
|
R/R AML: combination with trametinib
|
1b
|
Recruiting
|
NCT02016729
|
R/R multiple myeloma: combination with carfilzomib, lenalidomide, dexamethasone
|
1
|
Not yet recruiting
|
NCT03031730
|
|
Advanced solid tumors or multiple myeloma
|
1
|
Active not recruiting
|
NCT01723020
|
|
Metastatic cutaneous melanoma: combination with trametinib and dabrafenib or trametinib
|
1b/2a
|
Recruiting
|
NCT02110355
|
|
DS-3032b
|
Relapsed and/or refractory multiple myeloma
|
1
|
Recruiting
|
NCT02579824
|
Hematological malignancies: AML, ALL, CML and myelodysplastic syndrome
|
1
|
Recruiting
|
NCT02319369
|
|
Advanced solid tumors or lymphomas
|
1
|
Recruiting
|
NCT01877382
|
|
HDM201
|
Liposarcoma in combination with LEE011
|
1b/2
|
Recruiting
|
NCT02343172
|
Advanced solid and hematological tumors with wt-TP53
|
1
|
Recruiting
|
NCT02143635
|
|
Neuroblastoma: to match genomic aberrations at time of relapse to designed combined therapies
|
1
|
Recruiting
|
NCT02780128
|
|
CGM097
|
Advanced solid tumors with wt-TP53
|
1
|
Active not recruiting
|
NCT01760525
|
ALRN-6924
|
AML or advanced myelodysplastic syndrome with wt-TP53: alone or in combination with cytarabine
|
1/1b
|
Recruiting
|
NCT02909972
|
Advanced solid tumors or lymphomas with wt-TP53
|
1/2a
|
Recruiting
|
NCT02264613
|