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Therapy Name | Siremadlin |
Synonyms | |
Therapy Description |
Siremadlin (HDM201) binds to MDM2 and inhibits its interaction with p53, which prevents p53 degradation and potentially leads to restoration of p53 signaling and increased tumor cell death (PMID: 30899200, PMID: 27542305). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Siremadlin | HDM201|HDM-201|NVP-HDM201 | MDM2 Inhibitor 23 | Siremadlin (HDM201) binds to MDM2 and inhibits its interaction with p53, which prevents p53 degradation and potentially leads to restoration of p53 signaling and increased tumor cell death (PMID: 30899200, PMID: 27542305). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
TP53 wild-type | acute myeloid leukemia | predicted - sensitive | Siremadlin | Phase I | Actionable | In a Phase I trial, Siremadlin (HDM201) treatment demonstrated safety and resulted in overall response rates of 4.2% (1/24), 20% (3/15), and 22.2% (6/27) for the recommended expansion doses of 120 mg, 250 mg, and 45 mg, respectively, in patients with TP53 wild-type acute myeloid leukemia (PMID: 34862243; NCT02143635). | 34862243 |
TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | Siremadlin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, HDM201 treatment resulted in tumor regression in various cell line xenograft models of Tp53 wild-type tumors (Cancer Res 2016;76(14 Suppl):Abstract nr 4855). | detail... |
TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | Siremadlin | Phase I | Actionable | In a Phase I trial, Siremadlin (HDM201) treatment demonstrated safety and resulted in an overall response rate (ORR) of 3.5% (4/115; all partial responses) and disease control rate (DCR) of 36.5% in patients with TP53 wild-type advanced solid tumors, and at the recommended dose for expansion (120 mg), resulted in an ORR of 10.5% (3/29) and DCR of 44.8% in all patients, and a DCR of 83.3% (10/12) in patients with liposarcoma (PMID: 34862243; NCT02143635). | 34862243 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT02143635 | Phase I | Siremadlin | Study to Determine and Evaluate a Safe and Tolerated Dose of HDM201 in Patients With Selected Advanced Tumors That Are TP53wt | Completed | USA | NLD | FRA | ESP | DEU | 3 |
NCT02780128 | Phase I | Siremadlin Ceritinib + Ribociclib Trametinib | Next Generation Personalized Neuroblastoma Therapy | Terminated | USA | 0 |
NCT05447663 | Phase Ib/II | Siremadlin | A Study of Siremadlin Alone and in Combination With Donor Lymphocyte Infusion in Acute Myeloid Leukemia Post-allogeneic Stem Cell Transplant | Terminated | ITA | ESP | DEU | 0 |