Therapy Detail

Therapy Name Palbociclib + Trametinib
Therapy Description

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Palbociclib Ibrance PD0332991 CDK4/6 Inhibitor 8 Ibrance (palbociclib) is a selective inhibitor of cyclin-dependent kinase 4 (CDK4) and 6 (CDK6) (PMID: 19874578). Ibrance (palbociclib) is approved in combination with an aromatase inhibitor in postmenopausal patients with ER-positive, ERBB2 (HER2)-negative metastatic breast cancer, and in combination with Faslodex (fulvestrant) in patients with ER-positive, ERBB2 (HER2)-negative metastatic breast cancer (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 G13D colorectal cancer sensitive Palbociclib + Trametinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) synergistically inhibited growth of colorectal cancer cells harboring KRAS G13D in culture and resulted in partial tumor regression in patient-derived xenograft models (PMID: 26369631). 26369631
BRAF wild-type melanoma decreased response Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a BRAF wild-type melanoma cell line demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
NRAS wild-type melanoma decreased response Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, an NRAS wild-type melanoma cell line demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line with a BRAF mutation and loss of RB1 demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
KRAS mutant colorectal cancer sensitive Palbociclib + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) combination treatment resulted in objective response in PDX models of colorectal cancer cells harboring KRAS mutations (PMID: 26369631). 26369631
NRAS Q61K CDKN2A loss melanoma sensitive Palbociclib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Mekinist (trametinib) induced tumor regression in a mouse melanoma model expressing NRAS Q61K and harboring CDKN2A loss (PMID: 22983396). 22983396
BRAF mutant melanoma sensitive Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation demonstrated greater sensitivity to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture when compared to either agent alone (PMID: 27488531). 27488531
BRAF V600E KRAS wild-type colorectal cancer no benefit Palbociclib + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) combination treatment did not result in enhanced antitumor activity compared to Ibrance (palbociclib) alone in PDX models of KRAS wild-type colorectal cancer harboring BRAF V600E (PMID: 26369631). 26369631
Clinical Trial Phase Therapies Title Recruitment Status
NCT02065063 Phase I Palbociclib + Trametinib A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Anti-Cancer Activity of Trametinib in Combination With Palbociclib in Subjects With Solid Tumors Completed