Molecular Profile Detail

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Profile Name MDM2 amp TP53 wild-type
Gene Variant Detail

MDM2 amp (no effect)

TP53 wild-type (no effect)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
MDM2 amp TP53 wild-type osteosarcoma sensitive KRT-232 Preclinical Actionable In a preclinical study, KRT-232 (AMG 232) inhibited tumor growth in osteosarcoma cell line xenograft models with wild-type TP53 and MDM2 amplification (PMID: 25567130, PMID: 24967612). 24967612 25567130
MDM2 amp TP53 wild-type osteosarcoma sensitive SAR405838 Preclinical - Cell line xenograft Actionable In a preclinical study, SAR405838 inhibited growth of TP53 wild-type, MDM2 amplified osteosarcoma in culture and resulted in tumor regression in cell line xenograft models (PMID: 25145672). 25145672
MDM2 amp TP53 wild-type osteosarcoma sensitive Doxorubicin + KRT-232 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of KRT-232 (AMG 232) and Adriamycin (doxorubicin) inhibited tumor growth and induced tumor regression in an MDM2-amplifed TP53 wild-type osteosarcoma cell line xenograft model, with increased efficacy over either agent alone (PMID: 25567130). 25567130
MDM2 amp TP53 wild-type liposarcoma sensitive SAR405838 Preclinical - Cell line xenograft Actionable In a preclinical study, SAR405838 decreased viability and induced cell cycle arrest in MDM2-amplified dedifferentiated liposarcoma cell lines with wild-type TP53 in culture, and induced TP53 pathway activation and tumor regression in xenograft models (PMID: 26475335). 26475335
MDM2 amp TP53 wild-type glioblastoma sensitive RG7112 Preclinical - Cell line xenograft Actionable In a preclinical study, glioblastoma multiforme (GBM) cell lines with amplification of MDM2 and wild-type TP53 demonstrated sensitivity to RG7112 in culture, resulting in decreased viability and restoration of Tp53 signaling, and treatment with RG7112 resulted in growth inhibition in MDM2-amplified TP53 wild-type GBM cell line xenograft models (PMID: 26482041). 26482041
MDM2 amp TP53 wild-type glioblastoma predicted - sensitive KRT-232 Phase I Actionable In a Phase I trial, KRT-232 (AMG 232) demonstrated acceptable safety, and resulted in stable disease in 60% (6/10) of patients with TP53 wild-type, MDM2 amplified glioblastoma, with a median duration of 1.8 months (PMID: 31359240; NCT01723020). 31359240
MDM2 amp TP53 wild-type Advanced Solid Tumor predicted - sensitive KRT-232 Phase I Actionable In a Phase I trial, KRT-232 (AMG 232) demonstrated acceptable safety, and resulted in stable disease in 62.5% (10/16) of patients with TP53 wild-type, MDM2 amplified solid tumors other than liposarcoma, glioblastoma, and breast cancer, with a median duration of 3.3 months, and a patient with squamous cell carcinoma achieved unconfirmed partial response per central evaluation (PMID: 31359240; NCT01723020). 31359240
MDM2 amp TP53 wild-type Advanced Solid Tumor predicted - sensitive ALRN-6924 Phase I Actionable In a Phase I trial, treatment with ALRN-6924 resulted in a disease control rate of 71% (5/7) in advanced solid tumors patients with wild-type TP53 and MDM2 amplification (PMID: 34301750; NCT02264613). 34301750
MDM2 amp TP53 wild-type dedifferentiated liposarcoma predicted - sensitive BI 907828 Phase I Actionable In a Phase I trial, BI 907828 demonstrated activity in patients with TP53 wild-type, MDM2-amplified tumors, including a disease control rate (DCR) of 93% and progression-free survival greater than 10.5 months (PFS>10.5) in 5 of 11 dedifferentiated liposarcoma patients, a DCR of 88% and PFS>10.5 months in 4 of 8 well-differentiated liposarcoma patients (Ann Oncol (2022) 33 (suppl_7): S197-S224; NCT03449381). detail...
MDM2 amp TP53 wild-type well-differentiated liposarcoma predicted - sensitive BI 907828 Phase I Actionable In a Phase I trial, BI 907828 demonstrated activity in patients with TP53 wild-type, MDM2-amplified tumors, including a disease control rate (DCR) of 93% and progression-free survival greater than 10.5 months (PFS>10.5) in 5 of 11 dedifferentiated liposarcoma patients, a DCR of 88% and PFS>10.5 months in 4 of 8 well-differentiated liposarcoma patients (Ann Oncol (2022) 33 (suppl_7): S197-S224; NCT03449381). detail...