Therapy Detail
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| Therapy Name | LY3039478 |
| Synonyms | |
| Therapy Description |
LY3039478 is a pan-NOTCH inhibitor, which may limit growth and survival of cancer cells (Cancer Res April 15, 2013 73; 1131). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| LY3039478 | Crenigacestat|LY-3039478 | NOTCH Inhibitor (Pan) 5 | Crenigacestat (LY3039478) is a pan-NOTCH inhibitor, which may limit growth and survival of cancer cells (Cancer Res April 15, 2013 73; 1131, PMID: 32042099). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| NOTCH1 positive | ovarian cancer | sensitive | LY3039478 | Preclinical | Actionable | In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of ovarian cancer (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). | detail... |
| NOTCH1 positive | stomach cancer | sensitive | LY3039478 | Preclinical | Actionable | In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of gastric cancer (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). | detail... |
| Unknown unknown | leiomyosarcoma | not applicable | LY3039478 | Phase I | Actionable | In a Phase I trial, treatment with LY3039478 resulted in tumor necrosis in a patient with leiomyosarcoma (European Journal of Cancer, Volume 69, S15). | detail... |
| Unknown unknown | adenoid cystic carcinoma | not applicable | LY3039478 | Phase I | Actionable | In a Phase I trial, a patient with adenoid cystic carcinoma demonstrated a metabolic response when treated with LY3039478 (European Journal of Cancer, Volume 69, S15). | detail... |
| NOTCH1 positive | colon cancer | sensitive | LY3039478 | Preclinical | Actionable | In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of colon cancer (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). | detail... |
| NOTCH1 positive | breast cancer | sensitive | LY3039478 | Preclinical | Actionable | In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of breast cancer (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). | detail... |
| NOTCH1 positive | glioblastoma multiforme | sensitive | LY3039478 | Preclinical | Actionable | In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of glioblastoma (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). | detail... |
| FBXW7 mutant | Her2-receptor negative breast cancer | predicted - sensitive | LY3039478 | Phase I | Actionable | In a Phase I trial, LY3039478 treatment resulted in partial response lasted 9.5 months in a patient with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring FBXW7 mutation (PMID: 30060061; NCT01695005). | 30060061 |
| Unknown unknown | Advanced Solid Tumor | not applicable | LY3039478 | Phase I | Actionable | In a Phase I trial, treatment with LY3039478 was well-tolerated and demonstrated some preliminary efficacy in patients with advanced solid tumors (J Clin Oncol 33, 2015 (suppl; abstr 2533)). | detail... |
| Unknown unknown | Advanced Solid Tumor | not applicable | LY3039478 | Phase I | Actionable | In a Phase I trial, LY3039478 treatment resulted in 80% inhibition of plasma A-beta and more than 50% inhibition of Notch1-regulated genes in patients with advanced solid tumor, leading to partial response in 0.9% (1/110) and stable disease in 32.7% (36/110) of the patients (PMID: 30060061; NCT01695005). | 30060061 detail... |
| NOTCH1 positive | lung cancer | sensitive | LY3039478 | Preclinical | Actionable | In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of lung cancer (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). | detail... |
| Unknown unknown | testicular cancer | not applicable | LY3039478 | Phase I | Actionable | In a Phase I trial, a patient with testicular cancer demonstrated a metabolic response when treated with LY3039478 (European Journal of Cancer, Volume 69, S15). | detail... |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT02784795 | Phase I | Cisplatin + Gemcitabine + LY3039478 Carboplatin + Gemcitabine + LY3039478 LY3023414 + LY3039478 Abemaciclib + LY3039478 LY3039478 + Taladegib LY3039478 LY3023414 | A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors | Completed |
| NCT02518113 | Phase Ib/II | Dexamethasone LY3039478 | A Study of LY3039478 in Combination With Dexamethasone in Participants With T-ALL/T-LBL | Completed |
| NCT01695005 | Phase I | LY3039478 | A Study of LY3039478 in Participants With Advanced Cancer | Completed |
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