Therapy Detail

Therapy Name Trametinib
Synonym
Therapy Description

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Drug Name Trade Name Synonyms Drug Classes Drug Description
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
BRAF V600E MAP2K1 P124S melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 24265153). 24265153
BRAF F247L Advanced Solid Tumor sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing BRAF F247L demonstrated sensitivity to Mekinist (trametinib) in culture (PMID: 28512244). 28512244
BRAF V600E MAP2K1 Q56P melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P displayed reduced sensitivity to Mekinist (trametinib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). 22389471
FGFR2 dec exp KRAS mut lung cancer no benefit Trametinib Preclinical Actionable In a preclinical study, knocking down of Fgfr2 through shRNA did not sensitize KRAS mutant lung cancer cells to Mekinist (trametinib) induced growth inhibition in culture (PMID: 27338794). 27338794
KRAS mutant multiple myeloma resistant Trametinib Preclinical Actionable In a preclinical study, human multiple myeloma cells harboring mutant KRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
CTNNB1 mut NRAS mut liver cancer resistant Trametinib Preclinical Actionable In a preclinical study, human liver cancer cells harboring mutant NRAS and mutant CTNNB1 were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
STK11 inact mut Advanced Solid Tumor sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, the presence of an STK11 loss expression signature, which correlated to STK11 inactivating mutations, was associated with increased sensitivity to Mekinist (trametinib) in human tumor cell lines in culture (PMID: 27821489). 27821489
HRAS mutant endometrial cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human endometrial cancer cells harboring mutant HRAS in culture (PMID: 26343583). 26343583
KRAS mutant pancreatic adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of a majority (4/5) of human pancreatic adenocarcinoma cell lines harboring mutant KRAS in culture (PMID: 26343583). 26343583
NRAS mut NRAS Q61L melanoma predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61L demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
MAP2K1 Q56P lung adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, a lung adenocarcinoma cell line harboring MAP2K1 Q56P demonstrated sensitivity to Mekinist (trametinib), resulting in decreased cell viability (PMID: 26582713). 26582713
BRAF V600K melanoma sensitive Trametinib FDA approved Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011
AKT1 pos NRAS mut melanoma predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, one of two NRAS-mutant melanoma cell lines expressing AKT1 demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
FGFR3 dec exp KRAS mut lung cancer no benefit Trametinib Preclinical Actionable In a preclinical study, knocking down of Fgfr3 through shRNA did not sensitize KRAS mutant lung cancer cells to Mekinist (trametinib) induced growth inhibition in culture (PMID: 27338794). 27338794
BRAF L597S Advanced Solid Tumor sensitive Trametinib Preclinical Actionable Preclinical studies demonstrated the MEK inhibitor, Mekinist (trametinib) caused decreased activation of MEK and ERK in cells expressing BRAF L597S (PMID: 22798288). 22798288
CDKN2A loss melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line with CDKN2A loss demonstrated sensitivity to Mekinist (trametinib) in culture, resulting in inhibition of cell growth (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation and RB1 loss demonstrated reduced sensitivity when treated with Mekinist (trametinib) in culture (PMID: 27488531). 27488531
KRAS amp MET del exon14 non-small cell lung carcinoma no benefit Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, Mekinist (trametinib) treatment did not result in apoptotic induction or inhibition of cell proliferation in non-small cell lung carcinoma patient-derived cells harboring KRAS amplification and a MET exon 14 splice site mutation (PMID: 30072474). 30072474
BRAF V600E NRAS A146T MAP2K1 P387S melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E and also had reduced sensitivity in comparison to cell lines harboring BRAF V600E and NRAS A146T in culture (PMID: 22389471). 22389471
KRAS mutant non-small cell lung carcinoma sensitive Trametinib Phase I Actionable In a Phase I trial, two non-small cell lung carcinoma patients harboring a KRAS mutation demonstrated a partial response when treated with Mekinist (trametinib) (PMID: 22805291). 22805291
KRAS mutant non-small cell lung carcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of non-small cell cancer cell lines harboring mutant KRAS in culture (PMID: 26343583). 26343583
MAP2K1 Q56P stomach cancer sensitive Trametinib Preclinical Actionable In a preclinical study, a gastric cancer cell line harboring MAP2K1 Q56P demonstrated sensitivity to Mekinist (trametinib), resulting in decreased cell viability (PMID: 26582713). 26582713
NRAS mut NRAS Q61K melanoma predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
GNAQ Q209L uveal melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, uveal melanoma cell lines harboring GNAQ Q209L demonstrated increased sensitivity to growth inhibition by Mekinist (trametinib) in culture, compared to cells with wild-type GNAQ (PMID: 22733540). 22733540
NRAS mutant autonomic nervous system neoplasm sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human autonomic ganglia cancer cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
FGFR1 dec exp KRAS wild-type lung cancer no benefit Trametinib Preclinical Actionable In a preclinical study, knocking down of Fgfr1 through shRNA did not sensitize KRAS wild-type lung cancer cells to Mekinist (trametinib) induced growth inhibition in culture (PMID: 27338794). 27338794
BRAF V600E MAP2K1 P124L melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 K59del melanoma resistant Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). 22389471
KRAS mutant lung squamous cell carcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of squamous cell lung carcinoma cells harboring mutant KRAS in culture (PMID: 26343583). 26343583
HRAS mutant transitional cell carcinoma resistant Trametinib Preclinical Actionable In a preclinical study, human urinary transitional cell carcinoma cells harboring mutant HRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
FGFR1 dec exp KRAS mut lung cancer sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) treatment demonstrated enhanced growth inhibition in KRAS mutant lung cancer cells with decreased Fgfr1 expression through shRNA knockdown in culture, and tumor regression in xenograft models (PMID: 27338794). 27338794
BRAF mutant lung adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
MAP2K1 Y134C KRAS Q61H lung adenocarcinoma no benefit Trametinib Preclinical Actionable In a preclinical study, treatment with Mekinist (trametinib) had no effect on a lung adenocarcinoma cell line co-harboring MAP2K1 Y134C and KRAS Q61H in culture (PMID: 26582713). 26582713
NRAS mutant central nervous system cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human central nervous system cancer cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
HRAS G12R KRAS G13R thyroid cancer sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of thyroid cancer cell lines harboring KRAS G13R and HRAS G12R in culture and in cell line xenograft models (PMID: 27222538). 27222538
BRAF V600E MAP2K1 L115P melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
KRAS mutant pancreatic ductal carcinoma resistant Trametinib Preclinical Actionable In a preclinical study, human pancreatic ductal carcinoma cell lines harboring mutant KRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF G596R colorectal cancer sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced Erk signaling and inhibited proliferation of a colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28783719). 28783719
GNAQ mutant uveal cancer no benefit Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) treatment resulted in stable disease as best response in 50% (3/6) of patients with uveal melanoma harboring GNAQ or GNA11 mutations (PMID: 22805292; NCT00687622). 22805292
BRAF dec exp KRAS G12C lung cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) treatment demonstrated enhanced growth inhibition and sustained inhibition of Erk signaling in lung cancer cells harboring KRAS G12C with decreased Braf expression through shRNA knockdown in culture (PMID: 27338794). 27338794
KRAS G12C pancreatic adenocarcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, a pancreatic adenocarcinoma cell line harboring KRAS G12C demonstrated sensitivity to growth inhibition by MEK inhibitors, including Mekinist (trametinib), in culture (PMID: 28957417). 28957417
Unknown unknown uveal melanoma no benefit Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) treatment resulted in stable disease as best response in 50% (8/16) of patients with uveal melanoma (PMID: 22805292; NCT00687622). 22805292
STK11 Q37* non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 Q37*, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
STK11 dec exp non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, knockdown of STK11 increased sensitivity to Mekinist (trametinib) in non-small cell lung cancer cell lines in culture and in xenograft models (PMID: 27821489). 27821489
BRAF K601E melanoma predicted - sensitive Trametinib Case Reports/Case Series Actionable In a Phase II trial, a melanoma patient harboring BRAF K601E demonstrated a partial response and a progression free survival of 32 weeks when treated with Mekinist (trametinib) (PMID: 23248257; NCT01037127). 23248257
BRAF K601E melanoma predicted - sensitive Trametinib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring BRAF K601E demonstrated a 48% reduction in lymphadenopathy when treated with Mekinist (trametinib) and after more than 36 months of treatment showed a complete response (PMID: 28344857). 28344857
NRAS mutant non-Hodgkin lymphoma resistant Trametinib Preclinical Actionable In a preclinical study, human non-Hodgkin lymphoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS mutant liver cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of liver cancer cell lines harboring mutant NRAS in culture (PMID: 26343583). 26343583
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
KRAS mutant endometrial cancer resistant Trametinib Preclinical Actionable In a preclinical study, human endometrial cancer cells harboring mutant KRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF mutant colorectal cancer resistant Trametinib Preclinical Actionable In a preclinical study, a majority of human colorectal cancer cell lines (4/7) harboring mutant BRAF were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF G466V non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of non-small cell lung cancer cell lines harboring BRAF G466V in culture (PMID: 28783719). 28783719
BRAF K601E Advanced Solid Tumor sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, the MEK inhibitor, Mekinist (trametinib) decreased activation of MEK and ERK in cells expressing BRAF K601E in culture (PMID: 22798288). 22798288
FGFR1 dec exp KRAS mut pancreatic cancer sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) treatment demonstrated enhanced growth inhibition of KRAS mutant pancreatic cancer cells with decreased Fgfr1 expression through shRNA knockdown in culture (PMID: 27338794). 27338794
NRAS mutant melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). 30819666
NRAS mutant melanoma sensitive Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) treatment resulted in stable disease in 29% (2/7) of patients with NRAS mutated melanoma (PMID: 22805292; NCT00687622). 22805292
CSF3R N610S Advanced Solid Tumor predicted - sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of transformed cells expressing CSF3R N610S in culture (PMID: 30348809). 30348809
NRAS mutant leukemia predicted - sensitive Trametinib Phase Ib/II Actionable In a Phase Ib/II clinical trial, treatment with Mekinist (trametinib) resulted in an overall response rate of 28% in RAS-mutant leukemia patients, with 12% (7/57) of patients achieving complete remission (ASH 2015 Annual Meeting, Abst 677). detail...
KRAS G12S lung cancer decreased response Trametinib Preclinical Actionable In a preclinical study, a lung adenocarcinoma cell line harboring KRAS G12S demonstrated a decreased response when treated with Mekinist (trametinib) in culture (PMID: 26582713). 26582713
BRAF G466E HRAS Q61K melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF G466E and HRAS Q61K in culture (PMID: 28783719). 28783719
KRAS mutant leukemia predicted - sensitive Trametinib Phase Ib/II Actionable In a Phase Ib/II clinical trial, treatment with Mekinist (trametinib) resulted in an overall response rate of 28% in RAS-mutant leukemia patients, with 12% (7/57) of patients achieving complete remission (ASH 2015 Annual Meeting, Abst 677). detail...
KRAS mutant gastric adenocarcinoma conflicting Trametinib Preclinical Actionable In a preclinical study, the effect of Mekinist (trametinib) on human gastric adenocarcinoma cell lines harboring mutant KRAS is conflicting as cell lines were both sensitive and insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF V600E MAP2K1 C121S melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
NRAS mutant lymphoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human lymphoma cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant sarcoma resistant Trametinib Preclinical Actionable In a preclinical study, human sarcoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
STK11 inact mut non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
BRAF V600E/K melanoma sensitive Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) resulted in complete response in 7% (2/30), partial response in 33% (10/30), and stable disease in 37% (11/30) of BRAF-mutant melanoma patients (PMID: 22805292; NCT00687622). 22805292
BRAF V600E/K melanoma sensitive Trametinib FDA approved Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011
NRAS mut CDKN2A mut acute lymphocytic leukemia resistant Trametinib Preclinical Actionable In a preclinical study, human acute lymphoblastic leukemia cells harboring NRAS and CDKN2A mutations were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF mut STAG2 dec exp melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cells resulted in decreased response to Mekinist (trametinib) in culture (PMID: 27500726). 27500726
KRAS mutant colorectal cancer sensitive Trametinib Phase I Actionable In a Phase I trial, of eight patients with colorectal cancer, three patients harbored a KRAS mutation and demonstrated stable disease when treated with Mekinist (trametinib) (PMID: 22805291). 22805291
STK11 E57fs non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 E57fs, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
MAP2K1 F53L colorectal cancer sensitive Trametinib Preclinical Actionable In a preclinical study, a colorectal cancer cell line harboring MAP2K1 F53L demonstrated sensitivity to Mekinist (trametinib) in culture, resulting in decreased cell viability (PMID: 26582713). 26582713
Unknown unknown oral squamous cell carcinoma not applicable Trametinib Phase II Actionable In a Phase II trial, Mekinist (trametinib) treatment in patients with oral cavity squamous cell carcinoma was associated with decreased phosphorylation of Erk1/2 and reduced CD44 expression, and resulted in a partial response in 65% (11/17), stable disease in 29% (5/17), and progressive disease in 1 patient (6%) (PMID: 28151720). 28151720
BRAF V600E MAP2K1 E203K melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V487_P492delinsA pancreatic cancer sensitive Trametinib Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was sensitive to Mekinist (trametinib) in culture, resulting in cell growth inhibition (PMID: 26732095). 26732095
GNA11 Q209L uveal melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, uveal melanoma cell lines harboring GNA11 Q209L demonstrated increased sensitivity to growth inhibition by Mekinist (trametinib) in culture, compared to cells with wild-type GNA11 (PMID: 22733540). 22733540
BRAF V600E MAP2K1 G128V melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Mekinist (trametinib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). 24265153
BRAF mut KRAS mut CDKN2A mut triple-receptor negative breast cancer resistant Trametinib Preclinical Actionable In a preclinical study, human triple negative breast cancer cells harboring mutant BRAF, KRAS, and CDKN2A were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF V600E colorectal cancer sensitive Trametinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring a BRAF V600E mutation had increased sensitivity to Mekinist (trametinib) compared to other colorectal cancer lines in culture (PMID: 25309914). 25309914
MAP2K1 K57N lymphatic system cancer sensitive Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with refractory Erdheim-Chester disease harboring a MAP2K1 K57N mutation had a sustained clinical response to Mekinist (trametinib) for over 6 months (PMID: 26566875). 26566875
BRAF mutant multiple myeloma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
FGFR1 dec exp KRAS mut colorectal cancer no benefit Trametinib Preclinical - Cell culture Actionable In a preclinical study, knocking down of Fgfr1 through shRNA did not sensitize KRAS mutant colorectal cancer cells to Mekinist (trametinib) induced growth inhibition in culture (PMID: 27338794). 27338794
KRAS G13D NRAS mut melanoma predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, four of four NRAS-mutant melanoma cell lines expressing KRAS G13D were resistant to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
NRAS mut STAG2 dec exp melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in NRAS mutated melanoma cell lines resulted in decreased response to Mekinist (trametinib) in culture (PMID: 27500726). 27500726
BRAF G466V colorectal cancer sensitive Trametinib Preclinical - Pdx Actionable In a preclinical study, treatment with Mekinist (trametinib) delayed tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). 28783719
BRAF N486_P490del pancreatic ductal adenocarcinoma predicted - sensitive Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) treatment resulted in partial response in a patient with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del 8 weeks after initiation of treatment and lasted for 6 months (PMID: 29903880). 29903880
BRAF V600K MAP2K1 P124L melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). 25370473
BRAF V600E melanoma sensitive Trametinib FDA approved Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011
NRAS mutant acute myeloid leukemia sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human acute myeloid leukemia cell lines harboring mutant NRAS in culture (PMID: 26343583). 26343583
KRAS G12V PTPN11 loss pancreatic ductal adenocarcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, CRISPR-Cas9-mediated knock-out of PTPN11 abolished reactivation of MAPK signaling in the presence of Mekinist (trametinib) in pancreatic ductal adenocarcinoma cells harboring KRAS G12V, resulted in enhanced growth inhibition in culture (PMID: 29808009). 29808009
BRAF wild-type melanoma sensitive Trametinib Phase I Actionable In a Phase I study, 10% (4/39) of wild-type BRAF melanoma patients had a partial response to Mekinist (trametinib) (PMID: 22805292; NCT00687622). 22805292
BRAF V600K MAP2K1 P124Q melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). 25370473
BRAF K601E BRAF S363F melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). 29903896
KRAS mutant Advanced Solid Tumor sensitive Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) reduced tumor formation in 36% (8/22) of solid tumor patients harboring KRAS mutations (PMID: 22805291). 22805291
HRAS G13R KRAS G12R SRC T341M thyroid cancer sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of Sprycel (dasatinib)-resistant thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M in culture and in cell line xenograft models (PMID: 27222538). 27222538
NRAS mutant transitional cell carcinoma decreased response Trametinib Preclinical Actionable In a preclinical study, human urinary tract transitional cell carcinoma cells harboring mutant NRAS were moderately sensitive to Mekinist (trametinib) growth inhibition in culture (PMID: 26343583). 26343583
STK11 K48fs non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 K48fs, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
BRAF V600E MAP2K1 I111N melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
MAP2K1 V60E melanoma resistant Trametinib Preclinical Actionable In a preclinical study, a melanoma cell line expressing MAP2K1 V60E demonstrated resistance to Mekinist (trametinib) in culture (PMID: 24265153). 24265153
KRAS mutant pancreatic cancer predicted - sensitive Trametinib Phase I Actionable In a Phase I trial, a pancreatic cancer patient harboring a KRAS mutation demonstrated a partial response when treated with Mekinist (trametinib) (PMID: 22805291). 22805291
KRAS G12V pancreatic ductal adenocarcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, GS-493 and Mekinist (trametinib) synergistically inhibited growth of pancreatic ductal adenocarcinoma cells harboring KRAS G12V in culture (PMID: 29808009). 29808009
BRAF G469A non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) induced apoptosis and inhibited growth of a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 25706985). 25706985
KRAS mutant lung adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of a majority (12/17) lung adenocarcinoma cell lines harboring mutant KRAS in culture (PMID: 26343583). 26343583
BRAF N486_P490del ovarian cancer sensitive Trametinib Preclinical Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to Mekinist (trametinib), resulting in inhibition of cell growth in culture (PMID: 26732095). 26732095
STK11 E199* non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 E199*, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
BRAF L597S melanoma predicted - sensitive Trametinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture, and resulted in tumor shrinkage in 75% (8/12) subcutaneous tumors in one patient-derived xenograft (PDX) model harboring BRAF L597S that also harbored a BRAF variant of unknown significance, BRAF R239Q, however, was not sufficient to induce tumor shrinkage in a second PDX model with BRAF L597S, resulting only in tumor growth delay (PMID: 29903896). 29903896
NRAS wild-type melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, an NRAS wild-type melanoma cell line demonstrated inhibition of cell growth when treated with Mekinist (trametinib) in culture (PMID: 27488531). 27488531
CSF3R N610H Advanced Solid Tumor predicted - sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of transformed cells expressing CSF3R N610H in culture (PMID: 30348809). 30348809
BRAF L485_P490delinsY non-small cell lung carcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was sensitive to Mekinist (trametinib), resulting in cell growth inhibition (PMID: 26732095). 26732095
BRAF V600K NRAS Q61K melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were 3-7 fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600K in culture (PMID: 22389471). 22389471
BRAF V600E thyroid cancer predicted - sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
KRAS G12R thyroid cancer sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) inhibited Erk activation and growth of thyroid cancer cells harboring KRAS G12R in culture, and reduced tumor size in cell line xenograft models (PMID: 26324075). 26324075
BRAF G466V NRAS Q61K non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) growth of a non-small cell lung cancer cell line harboring BRAF G466V and expressing NRAS Q61K in culture (PMID: 28783719). 28783719
NRAS mutant lung adenocarcinoma resistant Trametinib Preclinical Actionable In a preclinical study, human lung adenocarcinoma cell lines harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF D594G melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF D594G in culture (PMID: 28783719). 28783719
GNA11 mutant uveal melanoma no benefit Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) treatment resulted in stable disease as best response in 50% (3/6) of patients with uveal melanoma harboring GNAQ or GNA11 mutations (PMID: 22805292; NCT00687622). 22805292
BRAF mutant pancreatic adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF V600E MAP2K1 V211D melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF L597R Advanced Solid Tumor sensitive Trametinib Preclinical Actionable Preclinical studies demonstrated the MEK inhibitor, Mekinist (trametinib) caused decreased activation of MEK and ERK in cells expressing BRAF L597R (PMID: 22798288). 22798288
BRAF V600E NRAS A146T melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were >10-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
STK11 W332* non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations, such as STK11 W332*, demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). 27821489
NRAS mutant multiple myeloma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant ovarian cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of ovarian cancer cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
FGFR1 amp NRAS amp non-small cell lung carcinoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring both FGFR1 and NRAS amplification were resistant to Mekinist (trametinib) in culture (PMID: 28630215). 28630215
BRAF V600E MAP2K1 P162S melanoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). 24265154
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). 22389471
Unknown unknown pancreatic cancer not applicable Trametinib Phase I Actionable In a Phase I trial, 42% (11/26) of pancreatic cancer patients demonstrated a decrease in tumor formation when treated with Mekinist (trametinib) (PMID: 22805291). 22805291
KRAS G12D PTPN11 loss pancreatic ductal adenocarcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, CRISPR-Cas9-mediated knock-out of PTPN11 abolished reactivation of MAPK signaling in the presence of Mekinist (trametinib) in pancreatic ductal adenocarcinoma cells harboring KRAS G12D, resulted in enhanced growth inhibition in culture (PMID: 29808009). 29808009
BRAF L514V BRAF V600E melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Mekinist (trametinib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
Clinical Trial Phase Therapies Title Recruitment Status
NCT01467310 Phase I Trametinib Defining the Triple Negative Breast Cancer Kinome Response to GSK1120212 Completed
NCT03148275 Phase II Trametinib Trametinib in Treating Patients With Epithelioid Hemangioendothelioma That Is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery Recruiting
NCT02705963 Phase I Trametinib A Drug-Drug Interaction Study to Assess the Effect of Trametinib on the Pharmacokinetics of an Oral Contraceptive in Female Patients With Solid Tumors Recruiting
NCT03363217 Phase Ib/II Trametinib Trametinib for Pediatric Neuro-oncology Patients With Refractory Tumor and Activation of the MAPK/ERK Pathway. Recruiting
NCT02152995 Phase II Trametinib Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer Recruiting
NCT02580708 Phase Ib/II Trametinib Rociletinib A Phase 1/2 Study of the Safety and Efficacy of Rociletinib When Administered in Combination With Trametinib in Patients With Activating EGFR Mutation-positive Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Terminated
NCT03434262 Phase I Filgrastim + Gemcitabine + Pegfilgrastim + Ribociclib Trametinib Sonidegib Ribociclib Ribociclib + Trametinib Ribociclib + Sonidegib Molecularly-Driven Doublet Therapy for Recurrent CNS Malignant Neoplasms Recruiting
NCT02124772 Phase I Trametinib Dabrafenib + Trametinib Study to Investigate Safety, Pharmacokinetic (PK), Pharmacodynamic (PD) and Clinical Activity of Trametinib in Subjects With Cancer or Plexiform Neurofibromas and Trametinib in Combination With Dabrafenib in Subjects With Cancers Harboring V600 Mutations Recruiting
NCT03087071 Phase II Panitumumab Trametinib Panitumumab in Combination With Trametinib in Cetuximab-Refractory Stage IV Colorectal Cancer Recruiting
NCT02296112 Phase II Trametinib Trametinib in Treating Patients With Advanced Melanoma With BRAF Non-V600 Mutations Active, not recruiting
NCT03091257 Phase I Dabrafenib + Trametinib Dabrafenib Trametinib A Study of Dabrafenib and/or Trametinib in Patients With Relapsed and/or Refractory Multiple Myeloma Recruiting
NCT01827384 Phase II Adavosertib + Carboplatin Temozolomide + Veliparib Everolimus Trametinib Molecular Profiling-Based Targeted Therapy in Treating Patients With Advanced Solid Tumors Recruiting
NCT01376310 Phase II Docetaxel + Trametinib Erlotinib + Trametinib Trametinib Pemetrexed + Trametinib Carboplatin + Trametinib Nab-paclitaxel + Trametinib Gemcitabine + Trametinib Everolimus + Trametinib GSK1120212 Rollover Study Terminated
NCT02070549 Phase I Trametinib Trametinib in Treating Patients With Advanced Cancer With or Without Hepatic Dysfunction Recruiting
NCT01658553 Phase I Trametinib A Study to Look at the Electrical Activity of the Heart in Subjects With Solid Tumor Cancers, Before and After Receiving the Study Treatment, GSK1120212 Completed
NCT02016729 Phase I Trametinib AMG 232 A Phase 1b Study Evaluating AMG 232 Alone and in Combination With Trametinib in Acute Myeloid Leukemia Completed
NCT03232892 Phase II Trametinib Trametinib in Patients With Advanced Neurofibromatosis Type 1 (NF1)-Mutant Non-small Cell Lung Cancer Recruiting
NCT02257424 Phase Ib/II Trametinib The BAMM Trial: BRAF, Autophagy and MEK Inhibition in Metastatic Melanoma: A Phase I/2 Trial of Dabrafenib, Trametinib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma Recruiting
NCT01990196 Phase II Dasatinib Trametinib Degarelix + Enzalutamide Neoadjuvant Phase 2 Study Comparing the Effects of AR Inhibition With/Without SRC or MEK Inhibition in Prostate Cancer Active, not recruiting
NCT03190915 Phase II Trametinib Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia Recruiting
NCT02780128 Phase I HDM201 Ceritinib + Ribociclib Trametinib Next Generation Personalized Neuroblastoma Therapy Recruiting
NCT02015117 Phase I Trametinib Trametinib With or Without Whole Brain Radiation Therapy in Treating Patients With Brain Metastases Active, not recruiting
NCT01231594 Phase I Dabrafenib Trametinib A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors Completed
NCT03878524 Phase I Oxaliplatin Palbociclib Vemurafenib Sirolimus Tretinoin Celecoxib Ipilimumab Ruxolitinib Dasatinib Abiraterone Idelalisib Trametinib Imatinib Erlotinib Carboplatin Olaparib Panobinostat Bortezomib Afatinib Fluorouracil Vorinostat Pembrolizumab Leucovorin Enzalutamide Ponatinib Nivolumab Everolimus Sunitinib Cabazitaxel Cabozantinib Lenvatinib Pertuzumab Sorafenib Venetoclax Bevacizumab A Personalized Medicine Study for Patients With Advanced Cancer of the Breast, Prostate, Pancreas or Those With Refractory Acute Myelogenous Leukemia (SMMART) Not yet recruiting
NCT01725100 Phase I Trametinib A Study to Determine the Relative Bioavailability of the MEK Inhibitor, Trametinib, in Subjects With Solid Tumor Malignancies Completed
NCT02551718 Phase I Bosutinib Irinotecan Romidepsin Busulfan Melphalan Nilotinib Crizotinib Cytarabine Mitoxantrone Dasatinib Pazopanib Paclitaxel Clofarabine Hydroxyurea Tretinoin Carfilzomib Nelarabine Bexarotene Pentostatin Everolimus Cabozantinib Mercaptopurine Methotrexate Cladribine Thioguanine Daunorubicin Ponatinib Etoposide Afatinib Gefitinib Gemcitabine Regorafenib Arsenic trioxide Trametinib Imatinib Erlotinib Dabrafenib Decitabine Axitinib Azacitidine Ruxolitinib Fludarabine Lapatinib Ceritinib Sirolimus Sorafenib Lomustine Sunitinib Cabazitaxel Temsirolimus Topotecan Bortezomib Pralatrexate High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia Recruiting
NCT01935973 Phase II Trametinib Trametinib + Uprosertib Trametinib With or Without GSK2141795 in Treating Patients With Recurrent or Persistent Endometrial Cancer Active, not recruiting
NCT03340506 FDA approved Trametinib Dabrafenib Dabrafenib + Trametinib Dabrafenib and/or Trametinib Rollover Study Recruiting
NCT01979523 Phase II Trametinib Trametinib + Uprosertib Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma Completed
NCT01940809 Phase II Dabrafenib Trametinib Ipilimumab Ipilimumab With or Without Dabrafenib, and/or Trametinib in Treating Patients With Melanoma That is Metastatic or Cannot Be Removed By Surgery Active, not recruiting
NCT02881242 Phase II Trametinib Trametinib in Treating Patients With Progressive Metastatic Hormone-Resistant Prostate Cancer Recruiting
NCT02042443 Phase II Fluorouracil + Leucovorin Capecitabine Trametinib Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery Completed
NCT02140840 Phase II Trametinib A Phase II Open-Label, Multiple-Dose, Single Agent Study to Evaluate the Overall Response Rate of Orally Administered Trametinib Withdrawn
NCT02101788 Phase II Topotecan Letrozole + Paclitaxel + Pegylated liposomal-doxorubicin + Tamoxifen Trametinib Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer Active, not recruiting
NCT01553851 Phase II Trametinib GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer Completed
NCT02465060 Phase II Erdafitinib Copanlisib Trametinib Crizotinib Sunitinib Sapanisertib Nivolumab AZD4547 Dasatinib Pertuzumab + Trastuzumab Dabrafenib + Trametinib Binimetinib Adavosertib Osimertinib Palbociclib Afatinib Capivasertib Defactinib GSK2636771 Vismodegib Ado-trastuzumab emtansine Larotrectinib Taselisib Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) Recruiting
NCT01902173 Phase Ib/II Trametinib Dabrafenib + Uprosertib GSK2141795, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer Suspended