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 use in combination with Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (FDA.gov). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Cobimetinib | Cotellic | GDC-0973 | MEK inhibitor (Pan) 26 MEK1 Inhibitor 26 MEK2 Inhibitor 24 | 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 use in combination with Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600E MAP2K1 V258I | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V258I in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 R201C | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R201C in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 R201H | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R201H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 Q56_G61delinsR | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q56_G61delinsR was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| 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 |
| BRAF V600E MAP2K1 P162S | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P162S in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 L235H | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L235H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 Y229H | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Y229H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 P293S | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P293S in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 F53_Q58delinsL | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53_Q58delinsL was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E | melanoma | predicted - sensitive | Cobimetinib | Case Reports/Case Series | 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 |
| BRAF V600E MAP2K1 M146I | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 M146I in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 L115P | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 P124S | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 D67N | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D67N was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 K4N | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K4N in culture (PMID: 36442478). | 36442478 |
| MAP2K1 E41_L54del | Advanced Solid Tumor | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of transformed cells expressing MAP2K1 E41_L54del in culture (PMID: 32122926). | 32122926 |
| BRAF V600E MAP2K1 R291K | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R291K in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 D67N | colon adenocarcinoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 D67N was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 A14S | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 A14S in culture (PMID: 36442478). | 36442478 |
| MAP2K1 E102_I103del | histiocytosis | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a clinical case study, Cotellic (cobimetinib) resulted in dramatic clinical improvement and decreased variant allele frequency in a patient with mixed histiocytosis harboring MAP2K1 E102_I103del, with the patient remaining disease free at least 3 years after treatment initiation (PMID: 36406830). | 36406830 |
| BRAF fusion | Erdheim-Chester disease | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Cotellic (cobimetinib) treatment resulted in a partial response with a tumor reduction of 67% in a patient with Erdheim-Chester disease harboring a BRAF fusion, with the patient remaining on treatment for at least 22 months (PMID: 38922339; NCT01775072). | 38922339 |
| BRAF V600E MAP2K1 P264S | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P264S in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 D136N | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D136N in culture (PMID: 36442478). | 36442478 |
| 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 |
| BRAF V600E MAP2K1 M94I | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 M94I in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 R108Q | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R108Q in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 N382H | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 N382H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 S212N | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S212N in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 V93F | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V93F in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 R96K | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R96K in culture (PMID: 36442478). | 36442478 |
| PIK3CA mutant | Erdheim-Chester disease | sensitive | Cobimetinib | Guideline | Actionable | Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org). | detail... |
| BRAF V600E MAP2K1 A132V | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 A132V in culture (PMID: 36442478). | 36442478 |
| 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_P490del | ovarian cancer | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
| BRAF V600E MAP2K1 D303N | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D303N in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 S72G | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S72G in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 G128D | colon adenocarcinoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 G128D was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| 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 V211D | Advanced Solid Tumor | predicted - resistant | Cobimetinib | Preclinical - Biochemical | Actionable | In a preclinical study, Cotellic (cobimetinib) did not inhibit kinase activity of MAP2K1 V211D in an in vitro assay (PMID: 31227518). | 31227518 |
| BRAF V600E MAP2K1 K57N | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57N was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 R349K | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R349K in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 P326H | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P326H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 P124S | colon adenocarcinoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 V224M | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V224M in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 I99_K104del | colon adenocarcinoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 I99_K104del was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E CBL dec exp | high grade glioma | predicted - resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, glioma cell lines harboring BRAF V600E and siRNA mediated knockdown of CBL were resistant to treatment with Cotellic (cobimetinib) in culture (PMID: 34433654). | 34433654 |
| BRAF V600E MAP2K1 E203K | colon adenocarcinoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 E203K was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| 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 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 |
| BRAF V600E MAP2K1 P387S | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P387S in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 S327T | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S327T in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 P306H | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P306H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 S331R | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S331R in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 S200Y | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S200Y in culture (PMID: 36442478). | 36442478 |
| MAP2K1 mutant | Erdheim-Chester disease | sensitive | Cobimetinib | Guideline | Actionable | Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org). | detail... |
| BRAF V600E MAP2K1 E203K | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E203K was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 S231L | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S231L in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 F53I | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 F53I was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 K57T | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57T was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 S86A | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S86A in culture (PMID: 36442478). | 36442478 |
| 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 |
| BRAF V600E MAP2K1 S150F | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 S150F in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 V154I | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 V154I in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 G294E | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G294E in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 L115P | colon adenocarcinoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a colon adenocarcinoma cell line harboring BRAF V600E and expressing MAP2K1 L115P was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 K57E | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 K57E was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 I99_K104del | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I99_K104del was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF R506_K507insLLR | Advanced Solid Tumor | predicted - sensitive | Cobimetinib | Preclinical - Biochemical | Actionable | In a preclinical study, Cotellic (cobimetinib) treatment inhibited Erk signaling in cells expressing BRAF R506_K507insLLR in culture (PMID: 34108213). | 34108213 |
| BRAF V600E MAP2K1 Y134C | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Y134C in culture (PMID: 36442478). | 36442478 |
| 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 N486_P490del | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
| BRAF V600E MAP2K1 G79V | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G79V in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 G128D | melanoma | resistant | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 G128D was resistant to Cotellic (cobimetinib) in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 W247* | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 W247* in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 A76V | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 A76V in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 D336H | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D336H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 E367K | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E367K in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 Q58* | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q58* in culture (PMID: 36442478). | 36442478 |
| NRAS mutant | Erdheim-Chester disease | sensitive | Cobimetinib | Guideline | Actionable | Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org). | detail... |
| BRAF V600E MAP2K1 R49H | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 R49H in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 A106T | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 A106T in culture (PMID: 36442478). | 36442478 |
| BRAF V600E MAP2K1 N345T | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 N345T in culture (PMID: 36442478). | 36442478 |
| MAP2K1 Q56P | Erdheim-Chester disease | 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 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 | Erdheim-Chester disease | 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 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 |
| 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 |
| BRAF V600E MAP2K1 I310L | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I310L in culture (PMID: 36442478). | 36442478 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT04185831 | Phase II | Atezolizumab Niraparib Cobimetinib Everolimus | A MolEcularly Guided Anti-Cancer Drug Off-Label Trial (MEGALiT) | Active, not recruiting | SWE | 0 |
| NCT05238831 | Phase II | Vemurafenib Vinorelbine Palbociclib Irinotecan Alpelisib Capecitabine Atezolizumab Paclitaxel Entrectinib Cobimetinib Nab-paclitaxel Fulvestrant Carboplatin Olaparib Pertuzumab/trastuzumab/hyaluronidase-zzxf Niraparib Vismodegib Alectinib Letrozole Ado-trastuzumab emtansine Bevacizumab Eribulin Anastrozole | SMMART Adaptive Clinical Treatment (ACT) Trial | Withdrawn | 0 | |
| NCT02457793 | Phase I | Cobimetinib Ravoxertinib | A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors | Completed | USA | 0 |
| NCT02427893 | Phase III | Cobimetinib Vemurafenib | Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma | Withdrawn | USA | 0 |
| NCT04931342 | Phase II | Cobimetinib Ado-trastuzumab emtansine Ipatasertib + Paclitaxel Atezolizumab + Bevacizumab | A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors | Active, not recruiting | USA | TUR | ITA | GBR | FRA | ESP | DEU | CZE | CHE | CAN | AUS | 2 |
| NCT05159245 | Phase II | Vemurafenib Tepotinib Vismodegib Apalutamide Alectinib Regorafenib Entrectinib Pertuzumab + Trastuzumab Pemigatinib Atezolizumab Cobimetinib Dabrafenib + Trametinib Dabrafenib Trametinib Abemaciclib | The Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs (FINPROVE) | Recruiting | FIN | 0 |
| NCT04079179 | Phase II | Cobimetinib | Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders (NACHO COBI) | Recruiting | USA | 0 |
| NCT04005690 | Phase II | Olaparib Cobimetinib | Cobimetinib or Olaparib in Treating Patients With Resectable Pancreatic Cancer | Recruiting | USA | 0 |
| NCT04591431 | Phase II | Everolimus Nivolumab Itacitinib Erlotinib Ponatinib Pemigatinib Ipatasertib Ipilimumab Cobimetinib Atezolizumab Palbociclib Entrectinib Vemurafenib Lapatinib Trastuzumab Brigatinib Alectinib Ado-trastuzumab emtansine Pertuzumab Vismodegib | The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy (ROME) | Active, not recruiting | ITA | 0 |
| NCT02639546 | Phase Ib/II | Cobimetinib | Safety and Pharmacokinetics of Cobimetinib in Pediatric and Young Adult Participants With Previously Treated Solid Tumors (iMATRIXcobi) | Completed | USA | ITA | ISR | GBR | FRA | ESP | DEU | 0 |
| NCT04801966 | Phase 0 | Palbociclib Alpelisib Atezolizumab Vemurafenib Ribociclib Talazoparib Cobimetinib Trametinib Abemaciclib Dabrafenib Nivolumab Binimetinib Pembrolizumab Encorafenib | Safety and Oversight of the Individually Tailored Treatment Approach: A Novel Pilot Study (TAILOR) | Terminated | AUS | 0 |
| NCT04409639 | Phase II | Cobimetinib | Cobimetinib in Newly Diagnosed or HMA-treated CMML Patients With RAS Pathway Mutations (CONCERTO) | Recruiting | USA | 0 |
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