Therapy Detail
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| Therapy Name | Crenolanib + Sorafenib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Crenolanib | CP-868596|CP-868,596 | FLT3 Inhibitor 61 PDGFR Inhibitor (Pan) 28 | Crenolanib (CP-868596) is a type III receptor tyrosine kinase inhibitor of PDGFR-alpha/beta and FLT3, which results in inhibition of downstream signaling and prevents growth in tumor cells (PMID: 22745105, PMID: 24227820, PMID: 29137311, PMID: 31309543). | |
| Sorafenib | Nexavar | BAY 43-9006 | CSF1R Inhibitor 28 FLT3 Inhibitor 61 KIT Inhibitor 55 PDGFR-beta Inhibitor 14 RAF Inhibitor (Pan) 23 RET Inhibitor 48 VEGFR2 Inhibitor 36 | Nexavar (sorafenib) is a multikinase inhibitor with activity against several kinases, including RAF kinases, VEGFR2, VEGFR3, PDGFR-beta, KIT, FLT3, RET, and CSF1R, potentially resulting in decreased tumor growth (PMID: 18445656, PMID: 15466206, PMID: 21517818). Nexavar (sorafenib) is FDA approved for metastatic differentiated thyroid carcinoma, hepatocellular carcinoma, and renal cell carcinoma (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | resistant | Crenolanib + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FLT3 D835Y was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on the combination of Crenolanib (CP-868596) and Nexavar (sorafenib) (PMID: 35344039). | 35344039 |
| FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | resistant | Crenolanib + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FLT3 F691L was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on the combination of Crenolanib (CP-868596) and Nexavar (sorafenib) (PMID: 35344039). | 35344039 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Crenolanib + Sorafenib | Clinical Study | Actionable | In a clinical study, combination Nexavar (sorafenib) and Crenolanib (CP-868596) resulted in 2 complete remissions, 1 complete remission with incomplete blood count recovery, and 1 partial response of 8 evaluable pediatric patients with relapsed or refractory FLT3 ITD-positive acute myeloid leukemia, and in preclinical studies, resulted in synergy in cell culture and improved leukemia response and survival in xenograft models compared to either agent alone (PMID: 35344039). | 35344039 |
| FLT3 exon 14 ins FLT3 D835A | acute myeloid leukemia | resistant | Crenolanib + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FLT3 D835A was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on the combination of Crenolanib (CP-868596) and Nexavar (sorafenib) (PMID: 35344039). | 35344039 |
| FLT3 exon 14 ins FLT3 N841K | acute myeloid leukemia | resistant | Crenolanib + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FLT3 N841K was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on the combination of Crenolanib (CP-868596) and Nexavar (sorafenib) (PMID: 35344039). | 35344039 |
| FLT3 exon 14 ins FLT3 N841Y | acute myeloid leukemia | resistant | Crenolanib + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FLT3 N841Y was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on the combination of Crenolanib (CP-868596) and Nexavar (sorafenib) (PMID: 35344039). | 35344039 |
| FLT3 exon 14 ins FLT3 D835N | acute myeloid leukemia | resistant | Crenolanib + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FLT3 D835N was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on the combination of Crenolanib (CP-868596) and Nexavar (sorafenib) (PMID: 35344039). | 35344039 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT02270788 | Phase I | Cytarabine + Leucovorin + Methotrexate Crenolanib + Sorafenib | Crenolanib in Combination With Sorafenib in Patients With Refractory or Relapsed Hematologic Malignancies | Completed | USA | 0 |
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