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Gene | BRAF |
Variant | V600K |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF V600K (previously reported as V599) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600K confers a gain of function to the Braf protein as demonstrated by increased kinase activity, downstream signaling, and the ability to transform cells in vitro (PMID: 15035987, PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF V600E/K BRAF V600K BRAF mutant BRAF V600X BRAF V600E/K BRAF V600K |
Transcript | NM_004333.6 |
gDNA | chr7:g.140753336_140753337delGTinsAA |
cDNA | c.1798_1799delGTinsAA |
Protein | p.V600K |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004333 | chr7:g.140753336_140753337delACinsTT | c.1798_1799delGTinsAA | p.V600K | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140753336_140753337delGTinsAA | c.1798_1799delGTinsAA | p.V600K | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140753336_140753337delACinsTT | c.1798_1799delGTinsAA | p.V600K | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140753336_140753337delGTinsAA | c.1798_1799delGTinsAA | p.V600K | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140753336_140753337delGTinsAA | c.1798_1799delGTinsAA | p.V600K | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140753336_140753337delACinsTT | c.1798_1799delGTinsAA | p.V600K | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140753336_140753337delGTinsAA | c.1798_1799delGTinsAA | p.V600K | RefSeq | GRCh38/hg38 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT05926960 | Phase II | Binimetinib + Encorafenib + Pembrolizumab Ipilimumab + Nivolumab | A Study Comparing 3 Study Medicines (Encorafenib, Binimetinib, Pembrolizumab) to 2 Study Medicines (Ipilimumab and Nivolumab) in Patients With Advanced Melanoma (PORTSIDE) | Active, not recruiting | SVK | POL | ITA | GBR | ESP | DEU | CZE | 0 |
NCT05270044 | Phase III | Binimetinib + Encorafenib | Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation. (COLUMBUS-AD) | Active, not recruiting | SWE | ROU | POL | NOR | NLD | ITA | HUN | GRC | GBR | FRA | ESP | DEU | CZE | CHE | CAN | BRA | BEL | AUT | AUS | ARG | 3 |
NCT03973918 | Phase II | Binimetinib + Encorafenib | Study of Binimetinib With Encorafenib in Adults With Recurrent BRAF V600-Mutated HGG (BRAF) | Terminated | USA | 0 |
NCT04759846 | Phase I | Binimetinib + Encorafenib | Hepatic Impairment Study of Encorafenib in Combination With Binimetinib in BRAF Melanoma | Withdrawn | ITA | ESP | CZE | 0 |
NCT04074096 | Phase II | Binimetinib + Encorafenib + Pembrolizumab | Binimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis (BEPCOME-MB) | Active, not recruiting | FRA | 0 |
NCT04310397 | Phase II | Dabrafenib + Trametinib Dabrafenib + Spartalizumab + Trametinib | Dabrafenib, Trametinib, and Spartalizumab for the Treatment of BRAF V600E or V600K Mutation Positive Stage IIIB/C/D Melanoma | Terminated | USA | 0 |
NCT04201457 | Phase Ib/II | Hydroxychloroquine + Trametinib Dabrafenib + Hydroxychloroquine + Trametinib | A Trial of Dabrafenib, Trametinib and Hydroxychloroquine for Patients With Recurrent LGG or HGG With a BRAF Aberration | Recruiting | USA | 0 |
NCT06194929 | Phase Ib/II | Defactinib + Encorafenib + RO5126766 Defactinib + RO5126766 | Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma (DETERMINE) | Recruiting | USA | 0 |
NCT05203172 | FDA approved | Encorafenib Binimetinib + Encorafenib Binimetinib + Encorafenib + Ribociclib Binimetinib + Cetuximab + Encorafenib Binimetinib | The FLOTILLA Study: Providing Continued Access to The Study Medicines Encorafenib and Binimetinib for Participants in Prior Clinical Trials | Recruiting | USA | SVK | NLD | ITA | ISR | HUN | GBR | FRA | ESP | DEU | CZE | CAN | BRA | AUS | 4 |
NCT02257424 | Phase Ib/II | Dabrafenib + Hydroxychloroquine + Trametinib | Dabrafenib, Trametinib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma (BAMM) | Completed | USA | 0 |
NCT06007924 | Phase II | Defactinib + RO5126766 | A Study of Avutometinib and Defactinib in People With Thyroid Cancer | Recruiting | USA | 0 |
NCT04657991 | Phase III | Pembrolizumab Binimetinib + Encorafenib + Pembrolizumab | A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma | Active, not recruiting | USA | TUR | SVK | POL | NZL | NOR | ITA | ISR | HUN | GRC | GBR | FRA | FIN | ESP | DEU | CZE | CHE | CAN | BRA | BGR | BEL | AUT | ARG | 4 |
NCT03878719 | Phase I | Binimetinib + Encorafenib | Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma | Terminated | ITA | 0 |
NCT05097378 | Phase II | Binimetinib + Encorafenib | Perioperative Encobini in BRAFV600 Mutant Stage III (B/C/D) or Oligometastatic Stage IV Melanoma (PREMIUM) | Unknown status | GBR | 0 |
NCT03915951 | Phase II | Binimetinib + Encorafenib | An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer | Active, not recruiting | USA | NLD | ITA | ESP | 1 |
NCT02465060 | Phase II | Nivolumab + Relatlimab Dabrafenib + Trametinib | Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) | Active, not recruiting | USA | 2 |
NCT03839342 | Phase II | Binimetinib + Encorafenib | Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations (BEAVER) | Active, not recruiting | CAN | 0 |
NCT03898908 | Phase II | Binimetinib + Encorafenib | Encorafenib and Binimetinib Before Local Treatment in Patients With BRAF Mutant Melanoma Metastatic to the Brain (EBRAIN-MEL) | Active, not recruiting | ESP | 0 |
NCT04557956 | Phase Ib/II | Tazemetostat Dabrafenib + Tazemetostat + Trametinib | Testing the Addition of the Anti-cancer Drug, Tazemetostat, to the Usual Treatment (Dabrafenib and Trametinib) for Metastatic Melanoma That Has Progressed on the Usual Treatment | Recruiting | USA | 0 |
NCT03235245 | Phase II | Binimetinib + Encorafenib Ipilimumab + Nivolumab | Immunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib (EBIN) | Active, not recruiting | POL | NLD | ITA | GBR | FRA | FIN | ESP | DNK | DEU | 0 |
NCT03864042 | Phase I | Caffeine + Dextromethorphan + Losartan + Midazolam + Omeprazole Modafinil Bupropion + Rosuvastatin Binimetinib + Encorafenib | Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors | Completed | USA | NLD | ESP | CAN | BEL | 0 |
NCT02130466 | Phase Ib/II | Dabrafenib + Trametinib Pembrolizumab + Trametinib Dabrafenib + Pembrolizumab Dabrafenib + Pembrolizumab + Trametinib | A Study of the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With Trametinib and Dabrafenib in Participants With Advanced Melanoma (MK-3475-022/KEYNOTE-022) | Completed | 0 | |
NCT01659151 | Phase II | Aldesleukin Fludarabine Vemurafenib | Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 Metastatic Melanoma | Active, not recruiting | USA | 0 |
NCT04551521 | Phase II | Atezolizumab Atezolizumab + Ipatasertib Atezolizumab + Pertuzumab + Trastuzumab Atezolizumab + Cobimetinib Alectinib Atezolizumab + Cobimetinib + Vemurafenib | CRAFT: The NCT-PMO-1602 Phase II Trial | Recruiting | DEU | 0 |
NCT03975231 | Phase I | Dabrafenib + Trametinib | Dabrafenib, Trametinib, and IMRT in Treating Patients With BRAF Mutated Anaplastic Thyroid Cancer | Recruiting | USA | 0 |
NCT02693535 | Phase II | Cobimetinib + Vemurafenib Atezolizumab + Talazoparib Regorafenib Larotrectinib Trastuzumab + Tucatinib Ipilimumab + Nivolumab Palbociclib Afatinib Entrectinib Talazoparib Pembrolizumab Temsirolimus Pertuzumab + Trastuzumab Atezolizumab + Pertuzumab/trastuzumab/hyaluronidase-zzxf Crizotinib Abemaciclib Sunitinib Olaparib | TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer (TAPUR) | Recruiting | USA | 0 |