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 23 | 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 | 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 |
| 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 | 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 | 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 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 | 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 | 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 |
| 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 | 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 |
| 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 |
| 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 | 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 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 | 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 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| 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 | POL | ITA | ISR | HUN | GBR | FRA | ESP | DEU | BEL | AUS | 1 |
| 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 | TUR | ROU | POL | LTU | ITA | ISR | HUN | HRV | GRC | GBR | FRA | ESP | DEU | CZE | CAN | BRA | BGR | AUS | ARG | 8 |
| 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 |
| NCT03669965 | Phase II | Ruxolitinib KRT-232 | KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera | Unknown status | USA | POL | HUN | FRA | ESP | DEU | 0 |
| NCT05797831 | Phase II | KRT-232 | Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer | Recruiting | USA | SWE | SVN | ROU | POL | NOR | LTU | ITA | ISR | HUN | FIN | EST | ESP | DNK | CAN | AUT | 1 |
| NCT03217266 | Phase I | KRT-232 | MDM2 Inhibitor AMG-232 and Radiation Therapy in Treating Patients With Soft Tissue Sarcoma | Active, not recruiting | USA | 0 |
| NCT05027867 | Phase II | KRT-232 | KRT-232 in Subjects With Relapsed or Refractory Small Cell Lung Cancer | Terminated | USA | HUN | FRA | ESP | DEU | AUS | 1 |
| NCT04878003 | Phase II | TL-895 KRT-232 | Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naive Myelofibrosis | Recruiting | USA | POL | BGR | 6 |
| NCT03107780 | Phase I | KRT-232 | Testing the Ability of AMG 232 (KRT 232) to Get Into the Tumor in Patients With Brain Cancer | Suspended | USA | 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 | BRA | AUS | 1 |
| NCT01723020 | Phase I | KRT-232 | A Phase 1 Study Evaluating AMG 232 in Advanced Solid Tumors or Multiple Myeloma | Completed | USA | NLD | FRA | 0 |
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