Therapy Detail
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| Therapy Name | Cobimetinib |
| Synonyms | |
| Therapy Description |
Cotellic (cobimetinib) is an allosteric inhibitor of MEK1/2, resulting in inhibition of extracellular signal-related kinase 2 (ERK2) phosphorylation and activation and decreased tumor cell proliferation (PMID: 22084396, PMID: 27956260). Cotellic (cobimetinib) is FDA approved for melanoma patients with BRAF V600E or V600K, in combination with Zelboraf (vemurafenib) (FDA.gov). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Cobimetinib | Cotellic | GDC-0973 | MEK inhibitor (Pan) 22 MEK1 Inhibitor 20 MEK2 Inhibitor 18 | Cotellic (cobimetinib) is an allosteric inhibitor of MEK1/2, resulting in inhibition of extracellular signal-related kinase 2 (ERK2) phosphorylation and activation and decreased tumor cell proliferation (PMID: 22084396, PMID: 27956260). Cotellic (cobimetinib) is FDA approved for melanoma patients with BRAF V600E or V600K, in combination with Zelboraf (vemurafenib) (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| MAP2K1 P105_I107del | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | 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, including a complete response in a patient with Erdheim-Chester disease harboring MAP2K1 P105_I107del (PMID: 30867592; NCT01953926). | 30867592 |
| Unknown unknown | Advanced Solid Tumor | not applicable | 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... |
| BRAF S363F BRAF K601E | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
| MAP2K1 Q56P | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Mekinist (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 stable disease in 6% (1/18) of patients, including a complete response in a patient with Erdheim-Chester disease harboring MAP2K1 Q56P (PMID: 30867592; NCT01953926). | 30867592 |
| MAP2K1 Q56P | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with refractory Erdheim-Chester disease harboring a MAP2K1 Q56P mutation had a reduction of lymphatic infiltrates to background within a month of receiving Cotellic (cobimetinib) therapy (PMID: 26566875). | 26566875 |
| BRAF L597S | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |
| MAP2K1 P124L | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | 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, including a complete response in a patient with mixed histiocytosis harboring MAP2K1 P124L (PMID: 30867592; NCT01953926). | 30867592 |
| Unknown unknown | lymphatic system cancer | not applicable | 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 |
| BRAF act mut | melanoma | sensitive | Cobimetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Cobimetinib (GDC-0973) induced cell death in human melanoma cell lines harboring BRAF activating mutations in culture and inhibited tumor growth in xenograft models (PMID: 22084396). | 22084396 |
| MAP2K1 P124Q | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | 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, including a complete response in a patient with Erdheim-Chester disease harboring MAP2K1 P124Q (PMID: 30867592; NCT01953926). | 30867592 |
| BRAF N486_T491delinsK | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | 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, including a complete response in a patient with Langerhans cell histiocytosis harboring BRAF N486_T491delinsK (PMID: 30867592; NCT01953926). | 30867592 |
| BRAF V600E | melanoma | sensitive | Cobimetinib | Phase I | Actionable | In a Phase I trial, Cotellic (cobimetinib) treatment resulted in a confirmed partial response in six melanoma patients harboring BRAF V600E (PMID: 27424159). | 27424159 |
| MAP2K1 E41_L54del | lung cancer | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of transformed human lung cells expressing MAP2K1 E41_L54del in culture (PMID: 32122926). | 32122926 |
| Unknown unknown | melanoma | not applicable | 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 |
| MAP2K1 V211D | Advanced Solid Tumor | predicted - resistant | Cobimetinib | Preclinical | Actionable | In a preclinical study, Cotellic (cobimetinib) did not inhibit kinase activity of MAP2K1 V211D in an in vitro assay (PMID: 31227518). | 31227518 |
| BRAF N486_T491delinsK | Advanced Solid Tumor | predicted - sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of transformed cells expressing BRAF N486_T491delinsK in culture (PMID: 30867592). | 30867592 |
| BRAF V600E | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | 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, including 1 partial response and 3 complete responses in 4 patients with Erdheim-Chester disease harboring BRAF V600E (PMID: 30867592; NCT01953926). | 30867592 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT02639546 | Phase Ib/II | Cobimetinib | Safety and Pharmacokinetics of Cobimetinib in Pediatric and Young Adult Participants With Previously Treated Solid Tumors (iMATRIXcobi) | Active, not recruiting |
| NCT04079179 | Phase II | Cobimetinib | Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders (NACHO COBI) | Not yet recruiting |
| NCT02322814 | Phase II | Paclitaxel Cobimetinib | A Study of Cobimetinib in Combination With Paclitaxel as First-line Treatment for Patients With Metastatic Triple-negative Breast Cancer | Active, not recruiting |
| NCT02427893 | Phase III | Cobimetinib Vemurafenib | Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma | Withdrawn |
| NCT04005690 | Phase II | Olaparib Cobimetinib | Cobimetinib or Olaparib in Treating Patients With Resectable Pancreatic Cancer | Recruiting |
| NCT02457793 | Phase I | Cobimetinib GDC-0994 | A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors | Completed |
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