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| Profile Name | BRAF L505H |
| Gene Variant Detail | |
| Relevant Treatment Approaches | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120 |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| Unknown unknown | Advanced Solid Tumor | no benefit | LY3009120 | LY3009120 | Phase I | Actionable | In a Phase I trial, LY3009120 did not achieve expected pharmacodynamic effects, resulted in stable disease as best overall response in 15.7% (8/51) of patients with advanced or metastatic cancer, and demonstrated no target inhibition (PMID: 31645440; NCT02014116). | 31645440 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | WX-554 | Phase I | Actionable | In a Phase I trial, WX-554 was well-tolerated and resulted in stable disease in 59% (20/34) and prolonged stable disease for greater than 6 months in 6% (2/34) of patients with advanced solid tumors (PMID: 27693888). | 27693888 |
| Unknown unknown | Advanced Solid Tumor | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Copanlisib + Refametinib | Phase I | Actionable | In a Phase I trial, Aliqopa (copanlisib) and Refametinib (BAY86-9766) combination treatment resulted in stable disease as best response in 33% (21/64) of patients with advanced solid tumors, however, the study failed to establish a tolerable and efficacious dose and schedule of this combination (PMID: 32314268; NCT01392521). | 32314268 |
| Unknown unknown | pancreatic cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Gemcitabine + Refametinib | Phase Ib/II | Actionable | In a Phase I/II trial, Refametinib (BAY86-9766) and Gemzar (gemcitabine) combination treatment resulted in an objective response rate of 23% and a disease control rate of 73% in patients with advanced pancreatic cancer (PMID: 27975152). | 27975152 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Refametinib | Phase I | Actionable | In a Phase I trial, Refametinib (BAY 86-9766) was well-tolerated and displayed some evidence of clinical benefit across several tumor types (PMID: 23434733). | 23434733 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Refametinib + Sorafenib | Phase I | Actionable | In a Phase I trial, the combination treatment of Refametinib (BAY86-9766) and Nexavar (sorafenib) in patients with advanced solid tumors resulted in a disease control rate of 65.8% (25/38), specifically, 2.6% (1/38) experienced a partial response and 63.2% (24/38) demonstrated stable disease (PMID: 26644411). | 26644411 |
| Unknown unknown | colorectal cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Refametinib + Sorafenib | Phase I | Actionable | In a Phase I trial, a patient with colorectal cancer demonstrated a durable partial response for 358 days when treated with the combination of Refametinib (BAY86-9766) and Nexavar (sorafenib) (PMID: 26644411). | 26644411 |
| Unknown unknown | hepatocellular carcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Refametinib + Sorafenib | Phase I | Actionable | In a Phase I trial, 43.8% (7/16) of hepatocellular carcinoma patients treated with a combination of Refametinib (BAY86-9766) and Nexavar (sorafenib) demonstrated stable disease (PMID: 26644411). | 26644411 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI-847325 | Phase I | Actionable | In a Phase I trial, BI-847325 demonstrated safety and some efficacy in a variety of advanced solid tumors (Mol Cancer Ther 2013;12(11 Suppl):B281). | detail... |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI-847325 | Phase I | Actionable | In a Phase I trial, BI-847325 treatment resulted in stable disease in 30% (21/69) of patients with advanced solid tumors, and one partial response for 67 days in a patient with esophageal cancer (PMID: 26650227). | 26650227 |
| Unknown unknown | esophageal cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI-847325 | Phase I | Actionable | In a Phase I trial, BI-847325 treatment resulted in stable disease in 30% (21/69) of patients with advanced solid tumors, and one partial response for 67 days in a patient with esophageal cancer (PMID: 26650227). | 26650227 |
| Unknown unknown | Hodgkin's lymphoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Darinaparsin + U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, Darinaparsin treatment in combination with U0126 inhibited Erk1/2 phosphorylation and led to enhanced apoptosis in Hodgkin's lymphoma cells compared to Darinaparsin treatment alone in culture (PMID: 25316819). | 25316819 |
| Unknown unknown | ovarian cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | ABT-737 + AZD8055 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of AZD8055 and Mekinist (trametinib) enhanced the sensitivity of ovarian cancer cells to ABT-737 in culture, resulting in greater apoptotic activity and cell cycle arrest when compared to Mekinist (trametinib) alone (PMID: 27980105). | 27980105 |
| Unknown unknown | ovarian cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | ABT-737 + Dactolisib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of BEZ235 and Mekinist (trametinib) enhanced the sensitivity of ovarian cancer cells to ABT-737 in culture, resulting in decreased cell viability (PMID: 27980105). | 27980105 |
| Unknown unknown | ovarian cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | ABT-737 + MK2206 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of MK2206 and Mekinist (trametinib) enhanced the sensitivity of ovarian cancer cells to ABT-737 in culture, resulting in decreased cell viability (PMID: 27980105). | 27980105 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Afuresertib + Trametinib | Phase I | Actionable | In a Phase I trial, the combination of Mekinist (trametinib) and Afuresertib (GSK2110183) was not well-tolerated in patients with advanced solid tumors (PMID: 25417902). | 25417902 |
| Unknown unknown | lung cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | AZ628 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Mekinist (trametinib) and AZ628 resulted in greater inhibition of Mek and apoptosis in a non-BRAF V600 mutant lung cancer cell line in culture compared to the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (J Clin Oncol 35, 2017 (suppl; abstr e23154)). | detail... |
| Unknown unknown | ovarian cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Buparlisib + Trametinib | Phase Ib/II | Actionable | In a Phase Ib trial, ovarian cancer patients demonstrated an objective response rate of 21% (6/21), including 1 complete response and 5 partial responses, to treatment with Buparlisib (BKM120) in combination with Mekinist (trametinib) (PMID: 25500057) | 25500057 |
| Unknown unknown | lung non-small cell carcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Docetaxel + Trametinib | Phase I | Actionable | In a Phase I/Ib trial, treatment with the combination of Mekinist (trametinib) and Taxotere (docetaxel) resulted in an overall response rate (ORR) of 21% (10/47, all partial responses) and stable disease in 43% (20/47) of patients with non-small cell lung cancer (PMID: 27876675). | 27876675 |
| Unknown unknown | lung squamous cell carcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Docetaxel + Trametinib | Phase I | Actionable | In a Phase I/Ib trial, treatment with the combination of Mekinist (trametinib) and Taxotere (docetaxel) resulted in partial response in 1 patient and stable disease in 3 patients within the subset of 5 evaluable patients with squamous non-small cell lung cancer patients (PMID: 27876675). | 27876675 |
| Unknown unknown | colorectal cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Fluorouracil + Trametinib | Preclinical | Actionable | In preclinical studies, Mekinist (trametinib) enhanced the efficacy of Adrucil (fluorouracil) in colorectal cancer cells in culture (PMID: 23438367). | 23438367 |
| Unknown unknown | breast cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Gemcitabine + Trametinib | Phase Ib/II | Actionable | In a Phase Ib clinical trial, the combination of Mekinist (trametinib) and Gemzar (gemcitabine) demonstrated safety and preliminary anti-tumor activity in patients with advanced solid tumors, including one complete response in a patient with breast cancer (PMID: 23583440). | 23583440 |
| Unknown unknown | pancreatic cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Gemcitabine + Trametinib | Phase Ib/II | Actionable | In a Phase Ib trial, a partial response was seen in 30% (3/11) of patients with pancreatic cancer after treatment with Mekinist (trametinib) in combination with Gemzar (gemcitabine) (PMID: 23583440). | 23583440 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Gemcitabine + Trametinib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination of Mekinist (trametinib) and Gemzar (gemcitabine) demonstrated safety and preliminary anti-tumor activity in patients with advanced solid tumors (PMID: 23583440). | 23583440 |
| Unknown unknown | pancreatic ductal adenocarcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Hydroxychloroquine + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Mekinist (trametinib) and Hydroxychloroquine in a patient with refractory metastatic pancreatic ductal adenocarcinoma resulted in a partial response, with a 95% decrease in the cancer antigen 19-9 after 2 months, and a 50% reduction in tumor burden at 4 months (PMID: 30833748). | 30833748 |
| Unknown unknown | melanoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | KRT-232 + Trametinib | Phase I | Actionable | In a Phase I trial, the combination therapy of KRT-232 (AMG 232) and Mekinist (trametinib) in 15 patients with metastatic cutaneous melanoma without a BRAF V600 mutation resulted in a partial response in 2 patients, stable disease in 11 patients, and progressive disease in 2 patients, and of the 15 patients, 11 experienced tumor reduction (J Clin Oncol 35, 2017 (suppl; abstr 2575)). | detail... |
| Unknown unknown | renal cell carcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pazopanib + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination of Mekinist (trametinib) and Votrient (pazopanib) effectively inhibited tumor angiogenesis and growth in cell line xenograft models of renal cell carcinoma (PMID: 26487278). | 26487278 |
| Unknown unknown | sarcoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pazopanib + Trametinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination of Votrient (pazopanib) and Mekinist (trametinib) demonstrated safety and resulted in partial response in 8% (2/25) and stable disease in 48% (12/25) of patients with advanced soft tissue sarcomas, but did not improve the 4 month progression-free survival rate over Votrient (pazopanib) alone (PMID: 28377484). | 28377484 |
| Unknown unknown | differentiated thyroid gland carcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pazopanib + Trametinib | Phase I | Actionable | In a Phase I trial, treatment with the combination of Votrient (pazopanib) and Mekinist (trametinib) was tolerable and resulted in an objective response rate of 33% (4/12, all partial responses), stable disease in 50% (5/12), a median progression-free survival (PFS) of 10.7 months, a 2-year PFS of 25%, and a median overall survival of 29.3 months in patients with differentiated thyroid cancer in the dose expansion cohort (PMID: 31186313; NCT01438554). | 31186313 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pazopanib + Trametinib | Phase I | Actionable | In a Phase I trial, combination treatment with Votrient (pazopanib) and Mekinist (trametinib) was tolerable and resulted in partial response in 12% (3/25), and stable disease in 72% (18/25) of patients with advanced solid tumors, and 9 patients remained on study for more than 6 cycles, including patients with differentiated thyroid cancer (n=3), colorectal cancer (n=2), melanoma (n=1), cholangiocarcinoma (n=1), ovarian cancer (n=1), and synovial cell sarcoma (n=1) (PMID: 31186313; NCT01438554). | 31186313 |
| Unknown unknown | lung non-small cell carcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pemetrexed Disodium + Trametinib | Phase I | Actionable | In a Phase I/Ib trial, treatment with the combination of Mekinist (trametinib) and Alimta (pemetrexed) resulted in an overall response rate of 14% (6/42, all partial responses) and stable disease in 55% (23/42) of patients with non-small cell lung cancer (PMID: 27876675). | 27876675 |
| Unknown unknown | renal cell carcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Sunitinib + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination of Mekinist (trametinib) and Sutent (sunitinib) effectively inhibited tumor angiogenesis and growth in cell line xenograft models of Sutent (sunitinib)-refractory renal cell carcinoma (PMID: 26487278). | 26487278 |
| Unknown unknown | pancreatic cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 |
| Unknown unknown | uveal melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 |
| Unknown unknown | oral squamous cell carcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 |
| Unknown unknown | endometrial cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Uprosertib | Phase I | Actionable | In a Phase I trial, Mekinist (trametinib) and Uprosertib (GSK2141795) combination treatment demonstrated increased toxicity and limited efficacy, resulted in no response (0/14) at RP2D dose and 1 response (8.3%, 1/12) at reduced dose in patients with recurrent endometrial cancer, with progression-free survival at 6 months in 14% and 25% of the patients, respectively (PMID: 31623857). | 31623857 |
| Unknown unknown | Advanced Solid Tumor | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Uprosertib | Phase I | Actionable | In a Phase I trial, the combination of Trametinib (GSK1120212) and Uprosertib (GSK2141795) was not well-tolerated and resulted in minimal efficacy in patients with advanced solid tumors (n=126), demonstrating an objective response rate of less than 5%, with one complete response and five partial responses (PMID: 32062691). | 32062691 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | RO4987655 | Phase I | Actionable | In a Phase I trial, RO4987655 demonstrated safety and preliminary clinical activity in Japanese patients with advanced solid tumors, including 1 partial response in a patient with esophageal cancer and 7 patients achieving progression-free survival for greater than 16 weeks (PMID: 25809858). | 25809858 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | RO4987655 | Phase I | Actionable | In a Phase I trial, RO4987655 demonstrated safety and preliminary efficacy in patients with advanced solid tumors (PMID: 22767668). | 22767668 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase I | Actionable | In a Phase I trial, Binimetinib (MEK162) treatment resulted in complete response in 1% (1/91), partial response in 2% (2/91), and stable disease with median duration of 3.94 months in 36% (33/91) of patients with advanced solid tumors (PMID: 28152546). | 28152546 |
| Unknown unknown | biliary tract cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase I | Actionable | In a Phase I trial, Binimetinib (MEK162) treatment resulted in complete response in 3.3% (1/30) and partial response in 6.7% (2/30) of patients with biliary tract cancer, with estimated progression free survival of 2.1 months and overall survival of 4.8 months (PMID: 28152546). | 28152546 |
| Unknown unknown | colorectal cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Fluorouracil + Leucovorin + Oxaliplatin | Phase I | Actionable | In a Phase I clinical trial, the combination of Binimetinib (MEK162) and FOLFOX chemotherapy demonstrated manageable toxicity and preliminary efficacy in metastatic colorectal cancer patients with chemotherapy resistance (J Clin Oncol 34, 2016 (suppl; abstr 2544)). | detail... |
| Unknown unknown | ovary epithelial cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Paclitaxel | Phase Ib/II | Actionable | In a Phase Ib trial, combination therapy with Taxol (paclitaxel) and Mektovi (binimetinib) was tolerable and resulted in an objective response rate of 18% (5/28, 1 complete response, 4 partial responses) and a clinical benefit rate of 57% (16/28, best overall response of stable disease or better) in patients with platinum resistant/refractory epithelial ovarian cancer, and clinical benefit was observed in all patients with MAPK pathway alterations (n=4) (PMID: 29844129; NCT01649336). | 29844129 |
| Unknown unknown | rhabdomyosarcoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | AZD8055 + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Koselugo (selumetinib) and AZD8055 worked synergistically to inhibit tumor growth in xenograft models of rhabdomyosarcoma (PMID: 23918606). | 23918606 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dacarbazine + Selumetinib | Phase I | Actionable | In a Phase I trial, the combination of Koselugo (selumetinib) and Deticene (dacarbazine) demonstrated safety and preliminary efficacy in patients with advanced solid tumors, with partial responses in 17% (4/23) and stable disease for greater than 6 weeks in 65% (15/23) of patients (PMID: 28264648). | 28264648 |
| Unknown unknown | Hodgkin's lymphoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Darinaparsin + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Darinaparsin treatment in combination with Koselugo (selumetinib) inhibited Erk1/2 phosphorylation and led to enhanced apoptosis in Hodgkin's lymphoma cells compared to Darinaparsin treatment alone in culture (PMID: 25316819). | 25316819 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Docetaxel + Selumetinib | Phase I | Actionable | In a Phase I trial, the combination of Koselugo (selumetinib) and Taxotere (docetaxel) demonstrated safety and preliminary efficacy in patients with advanced solid tumors, with partial responses in 22% (6/27) and stable disease for greater than 6 weeks in 52% (14/27) of patients (PMID: 28264648). | 28264648 |
| Unknown unknown | triple-receptor negative breast cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | KW-2450 + Selumetinib | Preclinical | Actionable | In a preclinical study, the combination of KW-2450 and Selumetinib worked synergistically to inhibit growth of triple-negative breast cancer cells in culture (PMID: 26443806). | 26443806 |
| Unknown unknown | pancreatic adenocarcinoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | MK2206 + Selumetinib | Phase II | Actionable | In a Phase II trial, the combination of Selumetinib (AZD6244) and MK2206 did not result in improved median overall survival compared to mFOLFOX therapy (3.9 mo vs. 6.7 mo) or improved median progression-free survival (1.9 mo vs 2.0 mo) in patients with pancreatic adenocarcinoma (PMID: 27978579). | 27978579 |
| Unknown unknown | breast cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase I | Actionable | In a Phase I trial, treatment with Selumetinib (AZD6244) demonstrated safety and preliminary efficacy patients with advanced solid tumors, including patients with breast cancer, with several patients achieving prolonged stable disease (PMID: 18390968). | 18390968 |
| Unknown unknown | uveal melanoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase II | Actionable | In a Phase II trial, Koselugo (selumetinib) improved median progression-free survival (15.9 vs 7 weeks, HR=0.46, p<0.001) but not overall survival (11.8 vs 9.1 months, HR=0.66, p=0.09) compared to chemotherapy in patients with uveal melanoma, but also caused high adverse event rate (PMID: 24938562; NCT01143402). | 24938562 |
| Unknown unknown | plexiform neurofibroma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | FDA approved | Actionable | In a Phase II trial (SPRINT) that supported FDA approval, Koselugo (selumetinib) treatment resulted in an objective response rate of 70% (35/50) in pediatric patients 2 years or older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas, with 28 of the responses lasted over 1 year (PMID: 32187457; NCT01362803). | 32187457 |
| Unknown unknown | triple-receptor negative breast cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the Mek inhibitor Selumetinib (AZD6244) inhibited tumorigenicity and invasiveness of triple-receptor negative breast cancer cell lines in culture and in cell line xenograft models (PMID: 26384399). | 26384399 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase I | Actionable | In a Phase I trial, treatment with Selumetinib (AZD6244) demonstrated safety and preliminary efficacy patients with advanced solid tumors, with several patients achieving prolonged stable disease (PMID: 18390968). | 18390968 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Clinical Study | Actionable | In a meta-analysis, Selumetinib (AZD6244) was shown to have modest clinical efficacy as a monotherapy in a variety of solid tumors (PMID: 24716986). | 24716986 |
| Unknown unknown | multiple myeloma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase II | Actionable | In a Phase II clinical trial, Selumetinib (AZD6244) demonstrated safety and tolerability but had minimal activity with a complete response achieved in 5.6% (2/36) of refractory multiple myeloma patients (PMID: 26446942). | 26446942 |
| Unknown unknown | triple-receptor negative breast cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib + SHP099 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination therapy of SHP099 and Selumetinib (AZD6244) led to decreased cell viability and reduced colony formation in triple-receptor negative breast cancer cells in culture and tumor regression in xenograft models (PMID: 30045908). | 30045908 |
| Unknown unknown | ovarian cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib + SHP099 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Selumetinib (AZD6244) and SHP099 resulted in decreased colony formation and reduced cell viability in ovarian cancer cells in culture and inhibition of tumor growth and reduced tumor angiogenesis in a patient-derived xenograft (PDX) model of ovarian cancer (PMID: 30045908). | 30045908 |
| Unknown unknown | pancreatic ductal adenocarcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib + SHP099 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the combination of SHP099 and Selumetinib (AZD6244) resulted in greater sensitivity compared to either agent alone in pancreatic ductal adenocarcinoma cells, demonstrating decreased cell viability and reduced colony formation in culture and decreased tumor growth in patient-derived xenograft (PDX) models (PMID: 30045908). | 30045908 |
| Unknown unknown | hepatocellular carcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib + Sorafenib | Phase II | Actionable | In a Phase II trial, Nexavar (sorafenib) and Selumetinib (AZD6244) combination treatment resulted in partial response in 15% (4/27) and stable disease in 48% (13/27) of hepatocellular carcinoma patients (PMID: 27681866). | 27681866 |
| Unknown unknown | colorectal cancer | not applicable | MEK inhibitor (Pan) | HL-085 + OKI-005 | Preclinical - Cell culture | Actionable | In a preclinical study, HL085 and OKI-005 demonstrated synergistic activity in 3 of 6 colorectal cancer cell lines, and increased immunogenicity of tumor cells in culture (Cancer Res 2019;79(13 Suppl):Abstract nr 4753). | detail... |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | AZD8330 | Phase I | Actionable | In a Phase I trial, AZD8330 demonstrated safety and some preliminary clinical activity in patients with advanced solid tumors (PMID: 23433846). | 23433846 |
| Unknown unknown | pancreatic cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Gemcitabine + Pimasertib | Preclinical | Actionable | In a preclinical study, treatment with Pimasertib (MSC1936369B) followed by Gemzar (gemcitabine) resulted in enhanced inhibition of proliferation and induction of apoptosis in pancreatic cell lines in culture (PMID: 26228206). | 26228206 |
| Unknown unknown | pancreatic adenocarcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Gemcitabine + Pimasertib | Phase I | Actionable | In a Phase I trial, Pimasertib in combination with Gemzar (gemcitabine) demonstrated safety and efficacy in metastatic pancreatic adenocarcinoma patients (PMID: 23846936). | 23846936 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib | Phase I | Actionable | In a Phase I trial, Pimasertib (MSC1936369B) demonstrated safety and some preliminary anti-tumor activity in patients with advanced solid tumors (J Clin Oncol 28:15s, 2010 (suppl; abstr 2504)). | detail... |
| Unknown unknown | ovarian cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + Voxtalisib | Phase II | Actionable | In a Phase II trial, the combination of Pimasertib (MSC1936369B) and XL765 (SAR245409) versus Pimasertib (MSC1936369B) alone resulted in an objective response rate (ORR) of 9.4% and 12.1%, and a median progression-free survival of 9.99 mo and 7.23 mo, respectively, in patients with ovarian carcinoma (n=65), and 18 pts treated with combination and 19 pts treated with single therapy discontinued the study, and thus, the study was terminated due to a low ORR and high rate of discontinuation (PMID: 31870556). | 31870556 |
| Unknown unknown | thyroid gland cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | SL327 + Sunitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of SL327 and Sutent (sunitinib) worked additively to decrease viability, induce apoptosis, and decrease migration of Taxotere (docetaxel)-resistant anaplastic thyroid cancer cell lines in culture, and to inhibit tumor growth in xenograft models (PMID: 28178630) | 28178630 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | TAK-733 | Phase I | Actionable | In a Phase I clinical trial, TAK-733 demonstrated safety and some preliminary efficacy in patients with advanced solid tumors with partial response in 5% (2/41) and stable disease in 37% (15/41) of patients (PMID: 27650277). | 27650277 detail... |
| Unknown unknown | melanoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Atezolizumab + Cobimetinib | Phase I | Actionable | In a Phase Ib trial, Tecentriq (atezolizumab) and Cotellic (cobimetinib) combination treatment demonstrated safety and preliminary clinical activity, resulted in a confirmed response in 41% (9/22) of patients with melanoma, regardless of KRAS/BRAF status (PMID: 30918950; NCT01988896). | 30918950 |
| Unknown unknown | colorectal cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Atezolizumab + Cobimetinib | Phase I | Actionable | In a Phase Ib trial, Tecentriq (atezolizumab) and Cotellic (cobimetinib) combination treatment resulted in partial response in 7% (7/84) of patients with metastatic colorectal cancer, with a median duration of response of 14.8 months, a disease control rate of 31% (26/84), a median progression-free survival of 1.9 months, and a median overall survival of 10.0 months (PMID: 30918950; NCT01988896). | 30918950 |
| Unknown unknown | colorectal cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Atezolizumab + Cobimetinib | Phase III | Actionable | In a Phase III trial (IMblaze370), Tecentriq (atezolizumab) and Cotellic (cobimetinib) combination treatment did not improve median overall survival (8.87 vs 8.51 months, HR=1.00, p=0.99) compared to Stivarga (regorafenib) in patients with chemotherapy-refractory metastatic colorectal cancer, 91.7% of whom were microsatellite stable or microsatellite instability-low (PMID: 31003911; NCT02788279). | 31003911 |
| Unknown unknown | lung non-small cell carcinoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Atezolizumab + Cobimetinib | Phase I | Actionable | In a Phase Ib trial, Tecentriq (atezolizumab) and Cotellic (cobimetinib) combination treatment demonstrated safety and preliminary clinical activity, resulted in a confirmed response in 18% (5/28) of patients with non-small cell lung cancer, regardless of KRAS/BRAF status (PMID: 30918950; NCT01988896). | 30918950 |
| Unknown unknown | melanoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Cobimetinib (GDC-0973) induced cell death in several human melanoma cell lines in culture and inhibited tumor growth in xenograft models (PMID: 22084396). | 22084396 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Phase I | Actionable | In a Phase I trial, Cotellic (cobimetinib) treatment resulted in stable disease for five months or more in five patients with advanced solid tumors (PMID: 27424159). | 27424159 detail... |
| Unknown unknown | lymphatic system cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Phase II | Actionable | In a Phase II trial, treatment with Cotellic (cobimetinib) in patients with histiocytic neoplasms resulted in a PET overall response rate of 89% (16/18), with complete response in 72% (13/18) and partial response in 17% (3/18), and resulted in stable disease in 6% (1/18) of patients, and at 11.9 months the median duration of response and progression-free survival were not yet reached (PMID: 30867592; NCT01953926). | 30867592 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Ipatasertib | Phase I | Actionable | In a Phase I clinical trial Ipatasertib (GDC-0068), in combination with the Mek inhibitor Cobimetinib (GDC-0973) demonstrated safety and preliminary efficacy in patients with advanced solid tumors (Cancer Res, October 1, 2014 74; CT328). | detail... |
| Unknown unknown | Advanced Solid Tumor | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Ravoxertinib | Phase I | Actionable | In a Phase Ib trial, treatment with the combination of Ravoxertinib (GDC-0994) and Cotellic (cobimetinib) in patients with advanced solid tumors resulted in stable disease in 29% (7/24) of patients and one unconfirmed partial response in a patient with pancreatic adenocarcinoma; however, the study was terminated due to intolerable toxicity of the treatment combination observed in patients (PMID: 32311798; NCT02457793). | 32311798 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Phase I | Actionable | In a Phase I trial, CI-1040 treatment resulted in median stable disease for 5.5 months in 28% (19/66) of patients with advanced solid tumors (including colorectal, non-small-cell lung, pancreatic, melanoma, and kidney) and partial response in 1 pancreatic cancer patient (PMID: 16009947). | 16009947 |
| Unknown unknown | glioblastoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI2536 + PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of BI 2536 and PD-0325901 resulted in greater inhibition of cell proliferation in glioblastoma cells in culture compared to treatment with either agent alone (PMID: 26573800). | 26573800 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Phase I | Actionable | In a Phase I clinical trial, PD-0325901 demonstrated preliminary clinical activity in patients with advanced solid tumors, however late-onset dose-limiting toxicities were encountered (PMID: 20215549). | 20215549 |
| Unknown unknown | colorectal cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Phase I | Actionable | In a Phase I study, PD-325901 demonstrated efficacy but toxicity at current dose was unacceptable (PMID: 21516509). | 21516509 |
| Unknown unknown | melanoma | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Phase I | Actionable | In a Phase I trial, PD-0325901 demonstrated some efficacy in previously treated melanoma patients, however, there was significant toxicity above 10 mg BID (PMID: 21516509). | 21516509 |
| Unknown unknown | breast cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Phase I | Actionable | In a Phase I trial, PD-0325901 demonstrated some efficacy, however, the dose administered resulted in a significant degree of toxicity (PMID: 21516509). | 21516509 |
| Unknown unknown | urinary bladder cancer | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 + PF-04691502 | Preclinical - Pdx | Actionable | In a preclinical study, PD-0325901, in combination with PF-04691502, delayed tumor growth in patient-derived xenograft models of bladder cancer (PMID: 24442130). | 24442130 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | RO5126766 | Phase I | Actionable | In a Phase I trial, RO5126766 demonstrated safety and some preliminary activity in Japanese patients with advanced solid tumors, with 42% (5/12) of patients achieving stable disease (PMID: 23860959). | 23860959 |
| Unknown unknown | Advanced Solid Tumor | not applicable | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | RO5126766 | Phase I | Actionable | In a Phase I trial, RO5126766 demonstrated safety and preliminary efficacy in patients with a variety of solid tumors (PMID: 22761467). | 22761467 |
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