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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 treatment demonstrated activity in patients with TP53 wild-type, MDM2-amplified dedifferentiated liposarcoma, resulting in a disease control rate (DCR) of 75% (9/12, all stable disease) and progression-free survival (PFS) ranging from 1.5 to 22 months, with PFS greater than 10.5 months in 41.6% (5/12) of patients (PMID: 37269344; NCT03449381). 37269344
MDM2 amp TP53 wild-type well-differentiated liposarcoma predicted - sensitive BI 907828 Phase I Actionable In a Phase I trial, BI 907828 treatment demonstrated activity in patients with TP53 wild-type, MDM2-amplified well-differentiated liposarcoma, resulting in a disease control rate of 100%, (7/7, 4 partial responses of at least 12 months, 3 stable disease), and a progression-free survival (PFS) of greater than 7.5 months, with a PFS of at least 14 months or more in 5 patients (PMID: 37269344; NCT03449381). 37269344
MDM2 amp TP53 wild-type heart sarcoma predicted - sensitive Milademetan Phase Ib/II Actionable In a Phase Ib/II trial, Milademetan treatment resulted in an overall response rate of 20% (2/10, both partial responses), a disease control rate of 60%, a median progression-free survival of 4.7 months, and a median overall survival of 12.2 months in patients with MDM2-amplified, TP53 wild-type intimal sarcoma (PMID: 37369013). 37369013
MDM2 amp TP53 wild-type Advanced Solid Tumor predicted - sensitive BI 907828 Phase I Actionable In a Phase I trial, BI 907828 treatment demonstrated safety and efficacy in patients with advanced solid tumors, resulting in a median progression-free survival of 8.1 months and an overall response rate of 11.1% (6/54, all partial responses (PR), 4 well-differentiated liposarcoma, 1 intrahepatic cholangiocarcinoma, 1 pancreatic cancer), with all PRs occurring in patients harboring an MDM2 amplification (PMID: 37269344; NCT03449381). 37269344
MDM2 amp TP53 wild-type glioblastoma sensitive BI 907828 Preclinical - Cell line xenograft Actionable In a preclinical study, BI 907828 treatment inhibited viability of a cell line derived from a TP53 wild-type, MDM2-amplified glioblastoma patient-derived xenograft (PDX) model in culture and inhibited tumor cell proliferation, induced apoptosis, and resulted in improved median survival compared to vehicle treatment (10 mg/kg treatment: 218 days and 2 mg/kg treatment: 57 days vs vehicle: 28 days, p<0.0001) in the PDX model, despite limited blood-brain barrier penetration (PMID: 37828724). 37828724
MDM2 amp TP53 wild-type malignant fibrous histiocytoma sensitive BI 907828 Preclinical - Pdx Actionable In a preclinical study, BI 907828 induced tumor regression in a patient-derived xenograft (PDX) model of MDM2-amplified, TP53 wild-type undifferentiated pleomorphic sarcoma (PMID: 39259562). 39259562
MDM2 amp TP53 wild-type lung squamous cell carcinoma sensitive BI 907828 Preclinical - Pdx Actionable In a preclinical study, BI 907828 induced prolonged tumor stasis and tumor regression in patient-derived xenograft (PDX) models of MDM2-amplified, TP53 wild-type squamous cell lung carcinoma (PMID: 39259562). 39259562
MDM2 amp TP53 wild-type intrahepatic cholangiocarcinoma predicted - sensitive BI 907828 Case Reports/Case Series Actionable In a Phase Ia/Ib trial, BI 907828 treatment resulted in a partial response in a patient with MDM2-amplified (CN=9), TP53 wild-type metastatic intrahepatic cholangiocarcinoma, with treatment lasting 12 months (PMID: 38567193; NCT03449381). 38567193
MDM2 amp TP53 wild-type ampulla of Vater adenocarcinoma predicted - sensitive BI 907828 Case Reports/Case Series Actionable In a Phase Ia/Ib trial, BI 907828 treatment resulted in a partial response in a patient with MDM2-amplified (CN=15) metastatic ampullary adenocarcinoma, with treatment ongoing at 19.1 months (PMID: 38567193; NCT03449381). 38567193
MDM2 amp TP53 wild-type intrahepatic cholangiocarcinoma predicted - sensitive BI 907828 + Ezabenlimab Case Reports/Case Series Actionable In a Phase Ia/Ib trial, treatment with the combination of BI 907828 and Ezabenlimab (BI 754091) resulted in 3 partial responses and 1 stable disease in 4 patients with MDM2-amplified, TP53 wild-type metastatic intrahepatic cholangiocarcinoma (PMID: 38567193; NCT03964233). 38567193
MDM2 amp TP53 wild-type gallbladder adenocarcinoma predicted - sensitive BI 907828 + Ezabenlimab Case Reports/Case Series Actionable In a Phase Ia/Ib trial, treatment with the combination of BI 907828 and Ezabenlimab (BI 754091) resulted in a partial response with a progression-free survival of 7.9 months in a patient with MDM2-amplified (CN=14), TP53 wild-type metastatic gallbladder adenocarcinoma (PMID: 38567193; NCT03964233). 38567193
MDM2 amp TP53 wild-type liposarcoma predicted - sensitive Alrizomadlin Case Reports/Case Series Actionable In a Phase I trial, Alrizomadlin (APG-115) treatment demonstrated safety in patients with advanced solid tumors, with an overall response rate of 10% (2/20, partial responses) and stable disease in 50% (10/20) of evaluable patients and a median progression-free survival (PFS) of 6.1 months, with an overall response rate of 25% (2/8) and disease control rate of 100% (8/8) in liposarcoma patients with wild-type TP53 and MDM2 amplification (PMID: 39002360). 39002360