Therapy Detail

Therapy Name Ponatinib + Trametinib
Synonym
Therapy Description

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Ponatinib Iclusig AP24534 BCR-ABL Inhibitor 24 DDR1 Inhibitor 8 DDR2 inhibitor 7 FGFR Inhibitor (Pan) 18 FLT3 Inhibitor 50 KIT Inhibitor 50 PDGFR-alpha Inhibitor 7 RET Inhibitor 36 SRC Inhibitor 27 VEGFR Inhibitor (Pan) 31 Iclusig (ponatinib) inhibits the Bcr-Abl fusion, and other tyrosine kinases, such as RET, DDR, VEGFR, FGFR, KIT, and FLT3 (PMID: 23526464, PMID: 25284748, PMID: 19878872). Iclusig (ponatinib) is FDA approved for chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph positive ALL) as well as ABL1 T315I CML and ABL1 T315I Ph positive ALL (FDA.gov).
Trametinib Mekinist GSK1120212 MEK inhibitor (Pan) 20 MEK1 Inhibitor 20 MEK2 Inhibitor 18 Mekinist (trametinib) inhibits MEK 1 and 2, which potentially leads to reduced tumor cell proliferation (PMID: 27956260). Mekinist (trametinib) is FDA approved for melanoma patients harboring BRAF V600E or BRAF V600K mutations, and in combination with Tafinlar (dabrafinib) for BRAF V600E/K-mutant melanoma, BRAF V600E- mutant non-small cell lung cancer, and BRAF V600E-mutant anaplastic thyroid cancer (FDA.gov).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KRAS mutant lung cancer sensitive Ponatinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Iclusig (ponatinib) synergistically inhibited proliferation of KRAS mutant lung cancer cells in culture and induced tumor regression in xenograft models (PMID: 27338794). 27338794
KRAS mutant colon cancer decreased response Ponatinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Iclusig (ponatinib) combination treatment was less efficient at inhibiting proliferation of KRAS mutant colon cancer cells in culture (PMID: 27338794). 27338794
KRAS G12D pancreatic cancer sensitive Ponatinib + Trametinib Preclinical Actionable In a preclinical study, the combination of Mekinist (trametinib) and Iclusig (ponatinib) induced cell death in tumors and prolonged survival in an animal model of pancreatic cancer harboring KRAS G12D (PMID: 27338794). 27338794
KRAS wild-type lung cancer decreased response Ponatinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Iclusig (ponatinib) combination treatment was less efficient at inhibiting proliferation of KRAS wild-type lung cancer cells in culture (PMID: 27338794). 27338794
KRAS mutant pancreatic cancer sensitive Ponatinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Iclusig (ponatinib) synergistically inhibited proliferation of KRAS mutant pancreatic cancer cells in culture (PMID: 27338794). 27338794
Clinical Trial Phase Therapies Title Recruitment Status
NCT03704688 Phase Ib/II Ponatinib + Trametinib Trial of Trametinib and Ponatinib in Patients With KRAS Mutant Advanced Non-Small Cell Lung Cancer Recruiting