Therapy Detail

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Therapy Name KRT-232
Synonyms
Therapy Description

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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Drug Name Trade Name Synonyms Drug Classes Drug Description
KRT-232 KRT 232|KRT232|AMG232|AMG 232|AMG-232|Navtemadlin MDM2 Inhibitor 22 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 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 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
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
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 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 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
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
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 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 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 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 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
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
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 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

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT03217266 Phase I KRT-232 MDM2 Inhibitor AMG-232 and Radiation Therapy in Treating Patients With Soft Tissue Sarcoma Active, not recruiting USA 0
NCT04878003 Phase II TL-895 KRT-232 Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naive Myelofibrosis Recruiting USA 8
NCT05027867 Phase II KRT-232 KRT-232 in Subjects With Relapsed or Refractory Small Cell Lung Cancer Terminated USA | FRA | ESP | DEU | AUS 2
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
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
NCT01723020 Phase I KRT-232 A Phase 1 Study Evaluating AMG 232 in Advanced Solid Tumors or Multiple Myeloma Completed USA | NLD | FRA 0
NCT03787602 Phase Ib/II Avelumab + KRT-232 KRT-232 Navtemadlin (KRT-232) With or Without Anti-PD-1/Anti-PD-L1 for the Treatment of Patients With Merkel Cell Carcinoma Recruiting USA | NLD | ITA | FRA | ESP | DEU | CAN | AUS 2
NCT05797831 Phase II KRT-232 Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer Recruiting USA | ITA | ESP | CAN | AUT 12
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 | ITA | GBR | FRA | ESP | DEU | CAN | AUS 20
NCT03669965 Phase II Ruxolitinib KRT-232 KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera Unknown status USA | FRA | ESP | DEU 2
NCT04113616 Phase Ib/II KRT-232 Decitabine + KRT-232 Cytarabine + KRT-232 An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 When Administered Alone and in Combination With Low-Dose Cytarabine (LDAC) or Decitabine in Patients With Acute Myeloid Leukemia (AML) Terminated USA | ITA | GBR | FRA | ESP | DEU | BEL | AUS 4


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