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Therapy Name | ASTX029 |
Synonyms | |
Therapy Description |
ASTX029 is an ERK1/2 inhibitor that prevents MAPK/ERK pathway activation, which may result in growth inhibition and tumor regression (PMID: 34330842). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
ASTX029 | ASTX-029|ASTX 029 | ERK Inhibitor (pan) 21 ERK1 Inhibitor 2 ERK2 Inhibitor 2 | ASTX029 is an ERK1/2 inhibitor that prevents MAPK/ERK pathway activation, which may result in growth inhibition and tumor regression (PMID: 34330842). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
NRAS G13D | melanoma | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, ASTX029 treatment inhibited growth of a melanoma cell line harboring NRAS G13D in culture (PMID: 34330842). | 34330842 |
BRAF V600E | melanoma | sensitive | ASTX029 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation, induced cell-cycle arrest, and inhibited growth of a melanoma cell line harboring BRAF V600E in culture and inhibited tumor growth in cell line xenograft models, and was also effective against cells with acquired resistance to Zelboraf (vemurafenib) or Koselugo (selumetinib) (PMID: 34330842). | 34330842 |
FLT3 exon 14 ins | acute myeloid leukemia | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cell lines harboring FLT3-ITD mutations were sensitive to treatment with ASTX029 in culture (PMID: 34330842). | 34330842 |
NRAS G12D | acute myeloid leukemia | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring NRAS G12D were sensitive to treatment with ASTX029 in culture (PMID: 34330842). | 34330842 |
NRAS G12D | melanoma | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, ASTX029 treatment inhibited growth of a melanoma cell line harboring NRAS G12D in culture (PMID: 34330842). | 34330842 |
BRAF V600D | melanoma | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, ASTX029 treatment inhibited growth of a melanoma cell line harboring BRAF V600D in culture (PMID: 34330842). | 34330842 |
BRAF V600E | colorectal adenocarcinoma | sensitive | ASTX029 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation and inhibited growth of colorectal adenocarcinoma cell lines harboring BRAF V600E in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 34330842). | 34330842 |
BRAF V600E NRAS Q61K | melanoma | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation and inhibited growth of a melanoma cell line harboring BRAF V600E and expressing NRAS Q61K in culture (PMID: 34330842). | 34330842 |
NRAS Q61R | melanoma | sensitive | ASTX029 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ASTX029 treatment inhibited growth of melanoma cell lines harboring NRAS Q61R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34330842). | 34330842 |
NRAS Q61L | acute myeloid leukemia | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring NRAS Q61L were sensitive to treatment with ASTX029 in culture (PMID: 34330842). | 34330842 |
NRAS Q61K | ovary adenocarcinoma | predicted - sensitive | ASTX029 | Case Reports/Case Series | Actionable | In a Phase II trial, ASTX029 treatment was well tolerated in patients with relapsed/refractory gynecological tumors harboring MAPK pathway alterations, and resulted in an objective response rate of 12.5% (4/32, all partial responses), a median duration of response of 8.5 months, and a median overall survival of 11.2 months, with a partial response in a patient with ovarian adenocarcinoma harboring NRAS Q61K who progressed on prior MEKi therapy (Ann Oncol (2024) 35 (Suppl_2): S591; NCT03520075). | detail... |
NRAS Q61K | melanoma | sensitive | ASTX029 | Preclinical - Pdx | Actionable | In a preclinical study, ASTX029 treatment inhibited growth of melanoma cell lines harboring NRAS Q61K in culture, and inhibited tumor growth in a patient-derived xenograft (PDX) model of melanoma harboring NRAS Q61K (PMID: 34330842). | 34330842 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT03520075 | Phase Ib/II | ASTX029 | Study of ASTX029 in Subjects With Advanced Solid Tumors | Active, not recruiting | USA | GBR | FRA | ESP | 0 |
NCT06284460 | Phase Ib/II | ASTX029 ASTX029 + Decitabine and Cedazuridine | Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms | Withdrawn | USA | 0 |