Therapy Detail

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Therapy Name KRT-232
Synonyms
Therapy Description

AMG 232 is a potent inhibitor of the MDM2-p53 interaction, and inhibits proliferation of tumor cells in a p53 dependent manner (PMID: 24456472).

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Drug Name Trade Name Synonyms Drug Classes Drug Description
KRT-232 KRT 232|KRT232|AMG232|AMG 232|AMG-232 MDM2 Inhibitor 20 KRT-232 (AMG 232) is a potent inhibitor of the MDM2-p53 interaction, and inhibits proliferation of tumor cells in a p53 dependent manner (PMID: 24456472, PMID: 32234759).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
TP53 wild-type lung cancer sensitive KRT-232 Preclinical - Cell culture Actionable In a preclinical study, KRT-232 (AMG 232) treatment activated Tp53 signaling and resulted in growth inhibition of TP53 wild-type lung cancer cell lines in culture (PMID: 26162687). 26162687
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
BRAF mut TP53 wild-type melanoma sensitive KRT-232 Preclinical - Cell line xenograft Actionable In a preclinical study, KRT-232 (AMG 232) inhibited growth of a melanoma cell line with wild-type TP53, that also harbored a BRAF mutation, in culture and inhibited tumor growth in a TP53 wild-type BRAF-mutant melanoma cell line xenograft model (PMID: 25567130). 25567130
TP53 wild-type melanoma sensitive KRT-232 Preclinical - Cell culture Actionable In a preclinical study, KRT-232 (AMG 232) treatment activated Tp53 signaling and resulted in growth inhibition of TP53 wild-type melanoma cells in culture (PMID: 26162687). 26162687
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 over exp TP53 wild-type ovarian clear cell carcinoma predicted - sensitive KRT-232 Preclinical - Cell culture Actionable In a preclinical study, KRT-232 (AMG 232) treatment sensitized ovarian clear cell carcinoma cell lines harboring wild-type TP53 and MDM2 overexpression to T-cell mediated killing when co-cultured with T-cells, demonstrating decreased cell viability (PMID: 32655895). 32655895
TP53 mutant Advanced Solid Tumor resistant KRT-232 Preclinical - Cell culture Actionable In a preclinical study, KRT-232 (AMG 232) did not inhibit growth of human tumor cell lines harboring TP53 mutations in culture (PMID: 25567130). 25567130
TP53 wild-type osteosarcoma sensitive KRT-232 Preclinical - Cell culture Actionable In a preclinical study, KRT-232 (AMG 232) treatment activated Tp53 signaling and resulted in growth inhibition of TP53 wild-type osteosarcoma cells in culture (PMID: 26162687). 26162687
BRAF V600E melanoma predicted - resistant KRT-232 Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft (PDX) models of melanoma harboring BRAF V600E demonstrated resistance to treatment with KRT-232 (AMG 232) (PMID: 32234759). 32234759
TP53 wild-type breast cancer sensitive KRT-232 Preclinical - Cell culture Actionable In a preclinical study, KRT-232 (AMG 232) activated Tp53 signaling, resulting in growth inhibition of TP53 wild-type breast cancer cells in culture (PMID: 26162687). 26162687
TP53 wild-type multiple myeloma 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 50% (5/10) of patients with TP53 wild-type multiple myeloma (PMID: 31359240; NCT01723020). 31359240
TP53 wild-type colon cancer sensitive KRT-232 Preclinical - Cell culture Actionable In a preclinical study, KRT-232 (AMG 232) treatment activated Tp53 signaling and resulted in growth inhibition of TP53 wild-type colon cancer cells in culture (PMID: 26162687). 26162687
TP53 wild-type liposarcoma 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 100% (10/10) of patients with TP53 wild-type well-differentiated liposarcomas (WDLPS) and 70% (7/10) of patients with TP53 wild-type de-differentiated liposarcomas, with median duration of 3.9 and 2.0 months respectively, and one patient with WDLPS achieved unconfirmed partial response per central evaluation (PMID: 31359240; NCT01723020). 31359240
TP53 wild-type estrogen-receptor positive breast cancer 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 83.3% (10/12) of patients with TP53 wild-type ER-positive breast cancer (BC), with a median duration of 2.0 months in ER-positive, PR-positive BC, 1.4 months in ER-positive, PR-negative BC, and one patient achieved unconfirmed partial response per central evaluation (PMID: 31359240; NCT01723020). 31359240
TP53 loss lung cancer resistant KRT-232 Preclinical - Cell culture Actionable In a preclinical study, TP53-null lung cancer cells were resistant to KRT-232 (AMG 232) induced growth inhibition in culture (PMID: 26162687). 26162687
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
TP53 wild-type lung non-small cell carcinoma sensitive KRT-232 Preclinical - Cell line xenograft Actionable In a preclinical study, KRT-232 (AMG 232) induced activation of Tp53 target genes and inhibited growth of a non-small cell lung cancer (NSCLC) cell line with wild-type TP53 in culture and inhibited tumor growth in a TP53 wild-type NSCLC cell line xenograft model (PMID: 25567130). 25567130
TP53 wild-type Advanced Solid Tumor sensitive KRT-232 Preclinical - Cell line xenograft Actionable In a preclinical study, KRT-232 (AMG 232) induced activation of Tp53 target genes and inhibited growth of several human tumor cell lines with wild-type TP53 in culture and in cell line xenograft models (PMID: 25567130). 25567130
TP53 wild-type Advanced Solid Tumor sensitive KRT-232 Phase I Actionable In a Phase I trial, KRT-232 (AMG 232) demonstrated acceptable safety, and resulted in stable disease in 80% (31/39) of patients with TP53 wild-type advanced solid tumors, with a median duration of 3.1 months (PMID: 31359240; NCT01723020). 31359240

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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT04878003 Phase II TL-895 KRT-232 Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naive Myelofibrosis Recruiting USA 6
NCT03662126 Phase II KRT-232 KRT-232 in Subjects With PMF, Post-PV MF, or Post-ET MF Who Have Failed a JAK Inhibitor Recruiting USA | CAN 10
NCT02016729 Phase I Trametinib KRT-232 A Phase 1b Study Evaluating AMG 232 Alone and in Combination With Trametinib in Acute Myeloid Leukemia Completed USA 0
NCT03107780 Phase I KRT-232 Testing the Ability of AMG 232 (KRT 232) to Get Into the Tumor in Patients With Brain Cancer Recruiting USA 0
NCT01723020 Phase I KRT-232 A Phase 1 Study Evaluating AMG 232 in Advanced Solid Tumors or Multiple Myeloma Completed USA 2
NCT03787602 Phase II KRT-232 This Study Evaluates KRT-232, a Novel Oral Small Molecule Inhibitor of MDM2, for the Treatment of Patients With (p53WT) Merkel Cell Carcinoma Who Have Failed Anti-PD-1/ PD-L1 Immunotherapy Unknown status USA 0
NCT03217266 Phase I KRT-232 MDM2 Inhibitor AMG-232 and Radiation Therapy in Treating Patients With Soft Tissue Sarcoma Recruiting USA 0
NCT03669965 Phase II Ruxolitinib KRT-232 KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera Active, not recruiting USA 5


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