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BIOMARKER:

BRAF V600K

i
Other names: BRAF, B-raf proto-oncogene, B-raf proto-oncogene, Serine/threonine kinase, V-Raf murine sarcoma viral oncogene homolog B, Serine/threonine-protein kinase B-Raf, Proto-oncogene B-Raf, BRAF1, RAFB1, B-raf proto-oncogene Serine/threonine-protein kinase, Murine sarcoma viral (V-Raf) oncogene homolog B1, B-raf serine/threonine-protein, 94 KDa B-raf protein, B-RAF1
Entrez ID:
Related biomarkers:
12h
BRAF V600K vs BRAF V600E: a clinical, dermoscopic, and response to immunotherapies and targeted therapies comparison. (PubMed, Clin Exp Dermatol)
Although the small entity of our case study, results underline similar clinical and dermoscopic characteristics between V600E and V600K mutations. Still, compared to BRAF V600E melanomas, the trend of BRAf V600k would be less responsive to the therapies adopted and with a worse prognosis.
Journal • IO biomarker
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF V600K
7d
Dabrafenib, Trametinib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma (clinicaltrials.gov)
P1/2, N=50, Completed, Abramson Cancer Center of the University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Oct 2026 --> Oct 2021 | Trial primary completion date: Oct 2024 --> Oct 2021
Clinical • Trial completion • Trial completion date • Trial primary completion date
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IL2 (Interleukin 2)
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BRAF V600E • BRAF V600 • BRAF V600K • BRAF V600R • BRAF V600D
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Mekinist (trametinib) • Tafinlar (dabrafenib) • hydroxychloroquine
8d
Improved pyrexia-related outcomes associated with an adapted pyrexia adverse event management algorithm in patients treated with adjuvant dabrafenib plus trametinib: Primary results of COMBI-APlus. (PubMed, Eur J Cancer)
The adapted pyrexia management algorithm appears to reduce the incidence of severe pyrexia outcomes, enables patients to manage pyrexia at home, and helps patients remain on treatment.
Clinical • Journal • Adverse events
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF V600K
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Mekinist (trametinib) • Tafinlar (dabrafenib)
15d
BECOME-MB: Binimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis (clinicaltrials.gov)
P2, N=150, Not yet recruiting, UNICANCER | Trial completion date: Sep 2028 --> Feb 2029 | Trial primary completion date: Sep 2024 --> Feb 2025
Clinical • Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • Mektovi (binimetinib) • Braftovi (encorafenib)
21d
Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma (clinicaltrials.gov)
P1/2, N=75, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022
Trial completion date • Trial primary completion date
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BCL2 (B-cell CLL/lymphoma 2)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mekinist (trametinib) • Tafinlar (dabrafenib) • navitoclax (ABT 263)
24d
Clinical • New P1/2 trial
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • cyclophosphamide • fludarabine IV • Contego (lifileucel)
2ms
Clinical • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib) • modafinil • bupropion • dextromethorphan • losartan potassium • omeprazole • rosuvastatin
2ms
DETECTION: Circulating Tumour DNA guidEd Therapy for Stage IIB/C mElanoma After surgiCal resecTION (clinicaltrials.gov)
P2/3, N=1050, Recruiting, The Christie NHS Foundation Trust | Not yet recruiting --> Recruiting
Enrollment open • Circulating tumor DNA
|
BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
|
BRAF V600E • BRAF V600 • BRAF V600K • NRAS Q61K • NRAS Q61R • NRAS G12D • NRAS G12 • NRAS Q61 • NRAS Q61L • BRAF V600R
|
Opdivo (nivolumab)
2ms
[VIRTUAL] Validation of a Rapid PCR-Based Assay for BRAF V600 Status for Prognostication and Therapeutic Selection in Colorectal Cancer Patients (AMP 2021)
Our results demonstrate that the Idylla BRAF Mutation Assay produces accurate, precise results in less than 3 hours, with faster TAT compared to NGS. Single-use cartridges eliminate the need for manual sample preprocessing and the risk of PCR contamination. In addition, this sensitive assay correctly identifies BRAF V600 alterations in samples with necrosis and low tumor cell content.
Clinical
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BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
|
BRAF V600E • NRAS mutation • BRAF V600 • BRAF V600K • BRAF K601E • BRAF V600R • BRAF L597Q • BRAF K601 • BRAF L597
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Idylla™ BRAF Mutation Test • Idylla™ NRAS-BRAF Mutation Test • TruSight Tumor 170 Assay
2ms
Treatment outcomes of patients with cutaneous melanoma harbouring rare BRAF mutations (NCRI 2021)
Conclusion Our results - on a small number of patients - suggest that patients with rare BRAF mutations may have inferior survival outcomes with first line targeted treatment, compared with patients with classical BRAF mutations. Impact statement Our findings add to the limited clinical knowledge on rare BRAF mutations in melanoma and may help guide treatment decisions on this small subset of patients.
Clinical • IO biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF mutation • BRAF V600K • BRAF K601E • BRAF D594G • BRAF V600R • BRAF D594N • BRAF L597S • BRAF T599 • BRAF V600_K601delinsE • BRAF K601 • BRAF L597
3ms
BRAF V600 Mutation Detection in Plasma Cell-Free DNA: NCCTG N0879 (Alliance). (PubMed, Mayo Clin Proc Innov Qual Outcomes)
In advanced melanoma, detectable cfDNA BRAF V600E/K mutation is present in about half the patients with stage IV with BRAF-mutant melanoma tumor tissue and appears to confer a poorer prognosis when detectable. Given the poorer prognosis, cfDNA can be used to risk-stratify patients with metastatic melanoma in practice or clinical trials.Trial Registration: clinicaltrials.gov Identifier: NCT00976573.
Journal
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BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
3ms
Clinical • New P2 trial
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib)
4ms
Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors (clinicaltrials.gov)
P1, N=42, Recruiting, Pfizer | Trial completion date: Aug 2022 --> Dec 2022 | Trial primary completion date: Aug 2021 --> Dec 2021
Clinical • Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib) • modafinil • bupropion • dextromethorphan • losartan potassium • omeprazole • rosuvastatin
4ms
BEAVER: Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations (clinicaltrials.gov)
P2, N=26, Recruiting, University Health Network, Toronto | Trial completion date: Sep 2021 --> Dec 2023 | Trial primary completion date: Sep 2021 --> Dec 2023
Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene) • KIAA1549
|
BRAF V600E • BRAF mutation • BRAF V600K • BRAF fusion • BRAF V600R • BRAF V600M • BRAF T599 • BRAF V600D • BRAF V600_K601delinsE • BRAF K601
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Mektovi (binimetinib) • Braftovi (encorafenib)
4ms
Enhancing Therapeutic Efficacy of Oncolytic Herpes Simplex Virus with MEK Inhibitor Trametinib in Some BRAF or KRAS-Mutated Colorectal or Lung Carcinoma Models. (PubMed, Viruses)
(3) A remarkably synergistic therapeutic efficacy was shown in vivo for BRAF wt/KRAS-mutated tumor models, when a combination of oHSV including PD-1 blockade and MEK inhibition. Collectively, these data provide some new insights for clinical development of combination therapy with oncolytic virus, MEK inhibition, and checkpoint blockade for BRAF or KRAS-mutated tumors.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
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BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • STAT1 (Signal Transducer And Activator Of Transcription 1)
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BRAF V600E • KRAS mutation • BRAF mutation • BRAF V600 • BRAF V600K
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Mekinist (trametinib)
4ms
Hepatic Impairment Study of Encorafenib in Combination With Binimetinib in BRAF Melanoma (clinicaltrials.gov)
P1, N=12, Not yet recruiting, Pierre Fabre Medicament | Initiation date: Feb 2021 --> Oct 2021
Clinical • Trial initiation date • Combination therapy
|
BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib)
5ms
Phase I/II trial of concurrent extracranial palliative radiation therapy with Dabrafenib and Trametinib in metastatic BRAF V600E/K mutation-positive cutaneous Melanoma. (PubMed, Clin Transl Radiat Oncol)
One serious AE was documented in relation to a grade 3 fever due to Dabrafenib and Trametinib requiring hospitalisation. The lack of grade 3 and 4 RT-related toxicities in our study suggests that Dabrafenib and Trametinib may be continued concurrently during fractionated non-visceral palliative RT to extracranial sites.
P1/2 data • Journal
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
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Mekinist (trametinib) • Tafinlar (dabrafenib)
5ms
[VIRTUAL] Validation of the Biocartis Idylla System for BRAF and KRAS mu- tations in formalin fixed tissues (ECP 2021)
The study has shown a 46% mutation rate for KRAS muta- tions in NSCLC samples, and with a KRAS G12C inhibitor on the hori- zon we have shown that it is feasible to use KRAS testing as a screening tool and for treatment stratification purposes in parallel. Results from the BRAF validation demonstrate the ability to detect mutations in the BRAF gene in a number of tissue types.
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase)
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BRAF V600E • KRAS mutation • BRAF V600 • KRAS G12D • KRAS G12V • BRAF V600K • KRAS G12A • KRAS exon 2 mutation • KRAS Q61H
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Idylla™ BRAF Mutation Test • Idylla™ KRAS Mutation Test
5ms
Impact of Prior Treatment on the Efficacy of Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma. (PubMed, Clin Cancer Res)
Patients previously treated with PD-1 or MAPK inhibition are significantly less likely to develop durable objective responses to ACT-TIL. While ACT-TIL is currently being investigated for treatment-refractory patients, it should also be considered as an initial treatment option for eligible patients with metastatic melanoma.
Clinical • Journal • Tumor-Infiltrating Lymphocyte • PD(L)-1 Biomarker • IO biomarker
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BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2)
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BRAF V600E • BRAF V600 • BRAF V600K
5ms
DETECTION: Circulating Tumour DNA guidEd Therapy for Stage IIB/C mElanoma After surgiCal resecTION (clinicaltrials.gov)
P2/3, N=1050, Not yet recruiting, The Christie NHS Foundation Trust | Initiation date: Jun 2021 --> Sep 2021
Trial initiation date • Circulating tumor DNA
|
BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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BRAF V600E • BRAF V600 • BRAF V600K • NRAS Q61K • NRAS Q61R • NRAS G12D • NRAS G12 • NRAS Q61 • NRAS Q61L • BRAF V600R
|
Opdivo (nivolumab)
6ms
Clinical • P3 data • PD(L)-1 Biomarker • IO biomarker
|
BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
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Keytruda (pembrolizumab) • Mektovi (binimetinib) • Braftovi (encorafenib)
6ms
[VIRTUAL] Regression tree analysis to identify factors associated with relapse-free survival (RFS) in patients with resected stage III BRAF V600E/K–mutant melanoma (ESMO 2021)
Background: The 5-y analysis of the Phase III COMBI-AD trial (NCT01682083) showed long-term RFS benefit with 12 months of adjuvant dabrafenib (dab) plus trametinib (tram) vs placebo (pbo) in patients with resected stage III BRAF V600E/K–mutant melanoma (5-y RFS rate, 52% vs 36%; hazard ratio, 0.51 [95% CI, 0.42-0.61]). These findings confirm and extend previous using regression tree analysis to identify subgroups that may particularly benefit from adjuvant therapy. Such analyses may inform treatment decisions.
Clinical • Tumor Mutational Burden
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BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden)
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BRAF V600E • BRAF V600 • BRAF V600K
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Mekinist (trametinib) • Tafinlar (dabrafenib)
7ms
A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies (clinicaltrials.gov)
P1/2, N=565, Completed, Sumitomo Dainippon Pharma Oncology, Inc | Active, not recruiting --> Completed
Clinical • Trial completion
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
BRAF V600E • HER-2 positive • BRAF V600 • HER-2 negative • ALK positive • BRAF V600K • ER negative • PGR negative
|
Abraxane (albumin-bound paclitaxel) • napabucasin (BBI608)
7ms
Clinical • Trial initiation date • Combination therapy • IO biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K • LDH elevation
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Mektovi (binimetinib) • Braftovi (encorafenib)
7ms
Clinical • Enrollment open • Combination therapy
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)
|
BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • BRAF V600K
|
Mekinist (trametinib) • DCC-3116
8ms
New P2/3 trial • Circulating tumor DNA
|
BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
|
BRAF V600E • BRAF V600 • BRAF V600K • NRAS Q61K • NRAS Q61R • NRAS G12D • NRAS G12 • NRAS Q61 • NRAS Q61L • BRAF V600R
|
Opdivo (nivolumab)
8ms
Clinical • New P1 trial • Combination therapy
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)
|
BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • BRAF V600K
|
Mekinist (trametinib) • DCC-3116
9ms
Encorafenib and Binimetinib Plus Pembrolizumab Versus Pembrolizumab for BRAF V600E/K Positive Melanoma (clinicaltrials.gov)
P3, N=624, Recruiting, Pfizer | Trial completion date: Dec 2029 --> May 2030 | Trial primary completion date: Aug 2023 --> Jan 2024
Clinical • Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • Mektovi (binimetinib) • Braftovi (encorafenib)
9ms
Phase I-II open label multicenter study of palbociclib + vemurafenib in BRAFV600MUT metastatic melanoma patients: uncovering CHEK2 as a major response mechanism. (PubMed, Clin Cancer Res)
Although the combination of palbociclib + fixed-dose vemurafenib did not allow an increased palbociclib dosage above 25mg, a significant clinical benefit was achieved in pretreated melanoma patients. An association between the transcriptomic data and clinical response was highlighted.
Clinical • P1/2 data • Journal
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CDKN2A (Cyclin-dependent kinase inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CHEK2 (Checkpoint kinase 2)
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BRAF V600E • BRAF V600 • BRAF V600K • RB1 expression • BRAF V600M
|
Zelboraf (vemurafenib) • Ibrance (palbociclib)
9ms
[VIRTUAL] Impact of BRAF mutations on outcomes in metastatic melanoma with central nervous system metastases treated with immune checkpoint inhibitors. (ASCO 2021)
Pts with BRAF-mutated mel with CNS mets receiving ICI had lower rates of progression in CNS and improved OS compared to other var . CRT was not associated with improved survival over non-concurrent RT . There has been significant improvement in OS of pts with mel CNS mets in the era of ICI and additional studies are warranted to understand the biology of BRAF var and the host immune system response in the CNS.
Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
9ms
[VIRTUAL] Evaluating clinical responses to BRAF inhibition in BRAF/TERT promoter mutated melanoma. (ASCO 2021)
This study is the first to report on outcomes of BRAF/MEK directed therapy in BRAF/TERT genetic duet vs BRAF mutated/TERT-WT melanomas in humans . While preclinical data from mouse models observed an improved response to BRAF/MEK inhibition in genetic duet tumors, no significant difference was observed . Our study is limited by small sample size .
Clinical • IO biomarker
|
TERT (Telomerase Reverse Transcriptase)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K • TERT promoter mutation • TERT mutation
9ms
[VIRTUAL] TMB and BRAF mutation status are independent predictive factors in stage IIIC/D/IV melanoma patients receiving adjuvant PD-1 antibodies. (ASCO 2021)
We identified TMB high as positive predictive marker in stage IIIC/D/IVmelanoma patients with adjuvant PD-1 antibody therapy . In tumors with BRAF V600E/K mutation and concurrent low TMB, adjuvant targeted therapy with BRAF- and MEK-inhibitors may be an alternative . This is also supported by the data on adjuvant dabrafenib and trametinib, which showed a greater advantage in patients with low TMB, presumably due to less tumor heterogeneity.
Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden)
|
BRAF V600E • TMB-H • BRAF mutation • BRAF V600K • TMB-L
|
Mekinist (trametinib) • Tafinlar (dabrafenib)
9ms
[VIRTUAL] Multicenter phase I/II trial of encorafenib with and without binimetinib in combination with nivolumab and low-dose ipilimumab in metastatic BRAF-mutant melanoma. (ASCO 2021)
Patients with symptomatic brain metastases will be included with an ECOG up to 2 and on ≤ 4mg of dexamethasone or equivalent . Continuous Bayesian toxicity monitoring will be used throughout to monitor DLT . Pre and on-treatment tumor biopsies will assess changes in the tumor microenvironment while peripheral blood ctDNA and T cell Ki67% changes will assess early response and immune activation during triplet and quadruplet therapy.
Clinical • P1/2 data • Combination therapy • PD(L)-1 Biomarker • IO biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K • LDH elevation
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Mektovi (binimetinib) • Braftovi (encorafenib) • dexamethasone
9ms
[VIRTUAL] Effects of baseline lactate dehydrogenase (LDH), interferon gamma (IFN-g) expression, and tumor mutational burden (TMB) on treatment response to first-line atezolizumab (A) + vemurafenib (V) and cobimetinib (C) in BRAFV600 mutation–positive advanced melanoma. (ASCO 2021)
IFN-g and TMB discriminated PFS benefit in pts receiving A+V+C but not for those receiving P+V+C . Durable responses were observed for pts treated with A+V+C in the n-LDH + h-IFNg subgroups.
Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • IFNG (Interferon, gamma)
|
BRAF V600E • BRAF V600 • BRAF V600K • PD-L1 negative • IFNG expression
|
Zelboraf (vemurafenib) • Tecentriq (atezolizumab) • Cotellic (cobimetinib)
9ms
A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies (clinicaltrials.gov)
P1/2, N=565, Active, not recruiting, Sumitomo Dainippon Pharma Oncology, Inc | Trial completion date: Dec 2021 --> Jun 2021
Clinical • Trial completion date
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
BRAF V600E • HER-2 positive • BRAF V600 • HER-2 negative • ALK positive • BRAF V600K • ER negative • PGR negative
|
Abraxane (albumin-bound paclitaxel) • napabucasin (BBI608)
9ms
[VIRTUAL] Correlation of BRAF Mutation Status in Circulating Tumor DNA with Tumor Biopsy and Clinical Outcomes in the COLUMBUS Study (HOPA 2021)
These findings confirm the reliability of ctDNA for detecting BRAF mutations; ctDNA may serve as an alternative test for detecting BRAF V600E/K mutations. The ctDNA BRAF mutations correlated with baseline markers of poor prognosis but not with the ORR.
Clinical • Clinical data • IO biomarker • Circulating tumor DNA
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
|
Zelboraf (vemurafenib) • Mektovi (binimetinib) • Braftovi (encorafenib)
9ms
[VIRTUAL] Synchronic melanoma or cutaneous metastasis: identification by mutational profile (EADO-WCM 2021)
Even though cutaneous metastasis may occur at the moment of diagnosis, dermoscopically reticular pattern is not the usual feature and it could misguide the diagnosis to second primary melanoma. Next generation sequencing could be useful to determine whether a skin lesion is metastatic or corresponds to another primary cutaneous melanoma. In our case, because the presence of uncommon (private) mutations in concordance in both tumors confirms the presentation of a primary cutaneous melanoma with a concomitant cutaneous metastasis.
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K • BRAF V600R • BRAF V600M • BRAF V600D • BRAF exon 15 mutation
9ms
[VIRTUAL] Tomatine exhibits antitumor potential in in vitro models of metastatic Melanoma (EADO-WCM 2021)
Collectively, our findings show that tomatine inhibits cell viability as well as MM cells invasiveness and displays valuable antiangiogenic and vascular disrupting effects only in experimental conditions that mimic a proangiogenic tumor microenvironment, by affecting the ER/p-eIF2α/ VEGF-axis.
Preclinical
|
HIF1A (Hypoxia inducible factor 1, alpha subunit) • MITF (Melanocyte Inducing Transcription Factor)
|
BRAF V600E • BRAF V600 • BRAF V600K • HIF1A expression
11ms
BRAF V600E/V600K mutations vs. non-standard alterations: Prognostic implications and therapeutic outcomes. (PubMed, Mol Cancer Ther)
Even so, 63% of patients with non-standard BRAF alterations achieved clinical benefit with BRAF/MEK inhibitors. Larger prospective studies are warranted in order to better understand the prognostic versus predictive implication of standard versus non-standard BRAF alterations.
Journal
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
11ms
Journal
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
11ms
[VIRTUAL] Treatment Experience and Pyrexia Management in a Patient With Stage III Melanoma Receiving Adjuvant BRAF/MEK-Targeted Therapy (ONS 2021)
A 38-year-old female patient with resected stage IIIB BRAF V600K mutant melanoma was started on adjuvant dabrafenib 150 mg BID and trametinib 2 mg QD following nodal recurrence after 3 cycles of adjuvant immunotherapy post-completion lymphadenectomy. Two weeks later, she presented with fever (maximum temperature, 102 F/39 C), grade 2 actinic rash, and grade 1/2 myalgias. Infectious workup was negative.
Clinical • IO biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mekinist (trametinib) • Tafinlar (dabrafenib)
11ms
Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor (clinicaltrials.gov)
P1, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2020 --> Feb 2023
Clinical • Enrollment closed • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • trebananib (AMG 386)
11ms
[VIRTUAL] A computation method for noise reduction based on ultra-deep targeted sequencing data (AACR 2021)
When using 1 ng DNA as input and at an expected MAF of 0.5%, only one mutation was missed, leading to a sensitivity of 97.73% (43/44) and 100% specificity. Furthermore, BinGo detected in the blood DNA sample a 15-bp EGFR exon 19 deletion at 0.05%.Bingo integrates UMI-bin derived variants and raw sequencing background noise modeling, enabling analysis of ultra-deep targeted NGS data for rare variant detection.
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene)
|
BRAF mutation • BRAF V600 • EGFR exon 19 deletion • BRAF V600K • BRAF V600R
11ms
[VIRTUAL] Nonclinical development of PF-07284890 (ARRY-461), a potent, brain-penetrant, small molecule inhibitor of BRAF V600-mutation-driven tumors in vitro and in vivo (AACR 2021)
GLP safety studies demonstrated a good safety profile for PF-07284890. PF‑07284890 is fully brain penetrant, with the potential to address this key unmet medical need and thereby defines a new class of brain penetrant, potent and selective BRAF inhibitors.
Preclinical
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
|
PF-07284890
11ms
BECOME-MB: Stereotactic Radiosurgery Added to Binimetinib and Encorafenib in Patients With BRAFV600 Melanoma With Brain Metastasis (clinicaltrials.gov)
P2, N=150, Not yet recruiting, UNICANCER | Trial completion date: Sep 2027 --> Sep 2028 | Trial primary completion date: Sep 2023 --> Sep 2024
Clinical • Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib)
11ms
Clinical • New P1 trial • Combination therapy
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib)
12ms
Clinical • Enrollment open • Combination therapy • IO biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K • LDH elevation
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Mektovi (binimetinib) • Braftovi (encorafenib)
12ms
Ipilimumab With or Without Dabrafenib, Trametinib, and/or Nivolumab in Treating Patients With Melanoma That Is Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
P1, N=15, Active, not recruiting, National Cancer Institute (NCI) | N=40 --> 15 | Trial primary completion date: Dec 2020 --> Jul 2020
Clinical • Enrollment change • Trial primary completion date • IO biomarker
|
ALB (Albumin)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Opdivo (nivolumab) • Mekinist (trametinib) • Tafinlar (dabrafenib) • Yervoy (ipilimumab) • CS1002 (ipilimumab biosimilar)
12ms
Clinical • Enrollment open
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • Mektovi (binimetinib) • Braftovi (encorafenib)
1year
Clinical • New P2 trial • PD(L)-1 Biomarker
|
TMB (Tumor Mutational Burden)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Zelboraf (vemurafenib) • Tecentriq (atezolizumab) • Cotellic (cobimetinib)
1year
Clinical • Trial primary completion date
|
BCL2 (B-cell CLL/lymphoma 2)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mekinist (trametinib) • Tafinlar (dabrafenib) • navitoclax (ABT 263)
1year
Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAF Mutant Melanoma That Cannot Be Removed by Surgery (clinicaltrials.gov)
P2, N=280, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Dec 2020 --> Dec 2021
Clinical • Trial primary completion date
|
ALB (Albumin)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mekinist (trametinib) • Tafinlar (dabrafenib)
1year
EBRAIN-MEL: Encorafenib and Binimetinib Before Local Treatment in Patients With BRAF Mutant Melanoma Metastatic to the Brain (clinicaltrials.gov)
P2, N=38, Recruiting, Grupo Español Multidisciplinar de Melanoma | Trial completion date: Apr 2022 --> Nov 2023 | Trial primary completion date: Oct 2020 --> Oct 2021
Clinical • Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib)
1year
Clinical • New P3 trial • PD(L)-1 Biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • Mektovi (binimetinib) • Braftovi (encorafenib)
1year
Clinical • New P1/2 trial • Combination therapy • PD(L)-1 Biomarker • IO biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K • LDH elevation
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Mektovi (binimetinib) • Braftovi (encorafenib)
1year
[VIRTUAL] Undifferentiated Spindle Cell Melanoma with USP6 Gene Rearrangement (ASDP 2020)
Our case highlights the importance of correlating molecular results with clinical context and microscopy. It also illustrates the difficulty of diagnosing poorly differentiated “sarcomatoid” melanoma.
Tumor Mutational Burden
|
TMB (Tumor Mutational Burden) • PRAME (Preferentially Expressed Antigen In Melanoma) • SOX10 (SRY-Box 10) • S100P (S100 calcium binding protein P)
|
BRAF V600E • TMB-H • BRAF V600 • BRAF V600K • PRAME expression
1year
[VIRTUAL] Deep Penetrating Nevus like Melanoma with Dysregulation of Beta-catenin and MAPK Pathways (ASDP 2020)
Imaging revealed pulmonary metastases and he was started on immunotherapy with dual checkpoint blockade (ipilimumab and nivolumab) with an excellent response. TERT promoter mutations have been shown with high specificity in borderline and malignant melanocytic lesions. Our case report depicts combinations of distinctive histology, immunohistochemistry (nuclear beta-catenin stain) and characteristic molecular signature (MAPK, beta-catenin, TERT mutations) that aptly fit for it to be called a “DPN like melanoma or melanoma with DPN features”.
PD(L)-1 Biomarker • IO biomarker
|
BRAF (B-raf proto-oncogene) • BAP1 (BRCA1 Associated Protein 1) • TERT (Telomerase Reverse Transcriptase)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
|
Opdivo (nivolumab) • Yervoy (ipilimumab)
1year
Clinical • Trial completion date
|
PTEN (Phosphatase and tensin homolog) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
|
Mekinist (trametinib) • Tafinlar (dabrafenib)
1year
Atypical UV Photoproducts Induce Non-canonical Mutation Classes Associated with Driver Mutations in Melanoma. (PubMed, Cell Rep)
Similar non-canonical mutations are present in skin cancers, which also display transcriptional asymmetry and dependence on NER. These include multiple driver mutations, most prominently the recurrent BRAF V600E and V600K substitutions, suggesting that mutations arising from rare, atypical UV photoproducts may play a role in melanomagenesis.
Journal
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
1year
Clinical • Trial completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Zelboraf (vemurafenib) • Mektovi (binimetinib) • Braftovi (encorafenib)
1year
Metanephric adenoma with BRAF V600K mutation and a doubtful radiological imaging: pitfalls in the diagnostic process. (PubMed, Med Mol Morphol)
Moreover, the histological diagnosis of this case was partially complicated by the equivocal immunohistochemical analysis showing negativity for BRAF VE1 staining. Only the mutational analysis demonstrated the presence of the BRAF V600K mutation (for the first time described in a case of metanephric adenoma), highlighting the necessity of sequencing in case of MA with negativity for BRAF VE1 clone.
Journal
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
1year
KEYNOTE B81: Brentuximab Vedotin With Pembrolizumab in Metastatic Solid Tumors (clinicaltrials.gov)
P2, N=60, Recruiting, Seagen Inc. | Not yet recruiting --> Recruiting
Clinical • Enrollment open • Combination therapy
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
BRAF V600E • EGFR mutation • BRAF V600 • BRAF V600K • ALK mutation
|
Keytruda (pembrolizumab) • Adcetris (brentuximab vedotin)
1year
Clinical • New P2 trial • Combination therapy
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
BRAF V600E • EGFR mutation • BRAF V600 • BRAF V600K • ALK mutation
|
Keytruda (pembrolizumab) • Adcetris (brentuximab vedotin)
over1year
A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies (clinicaltrials.gov)
P1/2, N=565, Active, not recruiting, Sumitomo Dainippon Pharma Oncology, Inc | Recruiting --> Active, not recruiting | Trial completion date: Mar 2021 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Jun 2021
Clinical • Enrollment closed • Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
BRAF V600E • HER-2 positive • BRAF V600 • HER-2 negative • ALK positive • BRAF V600K • ER negative • PGR negative
|
Abraxane (albumin-bound paclitaxel) • napabucasin (BBI608)
over1year
Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma. (PubMed, N Engl J Med)
In the 5-year follow-up of a phase 3 trial involving patients who had resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant therapy with dabrafenib plus trametinib resulted in a longer duration of survival without relapse or distant metastasis than placebo with no apparent long-term toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov number, NCT01682083; EudraCT number, 2012-001266-15.).
Clinical • Clinical Trial,Phase III • Journal
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mekinist (trametinib) • Tafinlar (dabrafenib)
over1year
[VIRTUAL] BRAF inhibitor encorafenib plus MEK inhibitor binimetinib is effective in leptomeningeal metastasis of melanoma (ADO 2020)
BRAF / MEK inhibitors such as encorafenib plus binimetinib are an effective treatment option for patients with symptomatic brain metastases and leptomeningeal metastases. However, the response time in the CNS is usually short. Current studies include BRAF / MEK inhibitors as sequence or combination therapy with immune checkpoint inhibitors for brain metastases and intrathecal therapy strategies for LMM were investigated.
IO biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib)
over1year
Mediastinal metastatic melanoma: an unusual case presentation of recurrent melanoma. (PubMed, BMJ Case Rep)
The patient was started on pembrolizumab with pending BRAF testing. V600E and V600K mutations in exon 15 of the BRAF gene were codetected, and the patient was treated with dabrafenib and trametinib.
Clinical • Journal • PD(L)-1 Biomarker
|
BRAF (B-raf proto-oncogene) • SOX10 (SRY-Box 10) • NCAM1 (Neural cell adhesion molecule 1)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • Mekinist (trametinib) • Tafinlar (dabrafenib)
over1year
Clinical • Trial completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib)
over1year
[VIRTUAL] Molecular Profiles of Metastatic Melanoma to the Brain Associated With Worse Survival (SSO 2020)
Mutations in BRAF V600K, GNAS and MET in patients with cutaneous melanoma and brain metastases are associated with worse overall survival. Our data suggest these patients may require a more aggressive or individualized treatment strategy. Further research should investigate additional prognostic factors associated with these mutations and development of new targeted therapies.
BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • GNAS (GNAS Complex Locus)
|
TP53 mutation • BRAF V600E • BRAF mutation • NRAS mutation • BRAF V600 • BRAF V600K • MET mutation
over1year
[VIRTUAL] Multidisciplinary Care of Melanoma of Unknown Primary: Experience in the Era of Molecular Profiling (SSO 2020)
Molecular profiling identified likely pathogenic mutations in 90% of MUP pts tested. More than half of pts with MUP did not go on to develop secondary metastatic sites, highlighting the unique biology of this disease, the value of molecular profiling, and the appropriate context of surgical resection in these patients. Immune surveillance in MUP remains under investigation but is likely important in preventing new metastatic disease.
TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • IL2 (Interleukin 2)
|
TP53 mutation • BRAF V600E • BRAF V600 • BRAF V600K • KIT mutation
over1year
[VIRTUAL] Mutational signatures induced by atypical UV photoproducts are associated with driver mutations in melanoma (ACS-Fall 2020)
We show that these novel mutation signatures are indeed caused by bulky UV photoproducts, as they show a striking transcriptional asymmetry that is modulated by nucleotide excision repair activity in both UV-exposed yeast and human skin cancers. We propose that mutations arising from atypical UV photoproducts may explain the origin of many driver mutations in skin cancer, including the recurrent BRAF V600E and V600K mutations in melanoma.
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
over1year
[VIRTUAL] Mutational signatures induced by atypical UV photoproducts are associated with driver mutations in melanoma (ACS-Fall 2020)
We show that these novel mutation signatures are indeed caused by bulky UV photoproducts, as they show a striking transcriptional asymmetry that is modulated by nucleotide excision repair activity in both UV-exposed yeast and human skin cancers. We propose that mutations arising from atypical UV photoproducts may explain the origin of many driver mutations in skin cancer, including the recurrent BRAF V600E and V600K mutations in melanoma.
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
over1year
Clinical • IO biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
over1year
[VIRTUAL] Correlation of BRAF mutation status in circulating tumour DNA (ctDNA) with tumour biopsy and clinical outcomes in COLUMBUS (ESMO 2020)
Methods In COLUMBUS part 1, 577 pts with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to encorafenib 450 mg QD + binimetinib 45 mg BID, encorafenib 300 mg QD or vemurafenib 960 mg BID. Funding: Pfizer. Clinical trial identification: NCT01909453; July 26, 2013.
Clinical • Clinical data • IO biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
|
Zelboraf (vemurafenib) • Mektovi (binimetinib) • Braftovi (encorafenib)
over1year
EBRAIN-MEL: Encorafenib and Binimetinib Before Local Treatment in Patients With BRAF Mutant Melanoma Metastatic to the Brain (clinicaltrials.gov)
P2, N=38, Recruiting, Grupo Español Multidisciplinar de Melanoma | Trial primary completion date: May 2020 --> Oct 2020
Clinical • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib)
over1year
BEAVER: Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations (clinicaltrials.gov)
P2, N=26, Recruiting, University Health Network, Toronto | Active, not recruiting --> Recruiting
Enrollment open • Circulating tumor DNA
|
BRAF (B-raf proto-oncogene) • KIAA1549
|
BRAF V600E • BRAF mutation • BRAF V600K • BRAF fusion • BRAF V600R • BRAF V600M • BRAF T599 • BRAF V600D • BRAF V600_K601delinsE • BRAF K601
|
Mektovi (binimetinib) • Braftovi (encorafenib)
over1year
Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor (clinicaltrials.gov)
P1, N=60, Recruiting, Dana-Farber Cancer Institute | Active, not recruiting --> Recruiting
Clinical • Enrollment open
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • trebananib (AMG 386)
over1year
COWBOY: Induction Therapy With Vemurafenib and Cobimetinib to Optimize Nivolumab and Ipilimumab Therapy (clinicaltrials.gov)
P2, N=200, Recruiting, Radboud University | Active, not recruiting --> Recruiting
Clinical • Enrollment open • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Opdivo (nivolumab) • Zelboraf (vemurafenib) • Yervoy (ipilimumab) • Cotellic (cobimetinib)
over1year
[VIRTUAL] Phase I study of 9-ing-41, a small molecule selective glycogen synthase kinase-3 beta (GSK-3β) inhibitor, as a single agent and combined with chemotherapy, in patients with refractory tumors. (ASCO 2020)
9-ING-41 is given intravenously (IV) twice-weekly as a single-agent (21-day cycle) or combined with gemcitabine, gemcitabine/nab-paclitaxel, carboplatin, carboplatin/paclitaxel, doxorubicin, lomustine or irinotecan in patients previously treated with the same chemotherapy. 9-ING-41 has dose-proportional PK, is well tolerated with significant antitumor activity as monotherapy and in combination with chemotherapy in pts with refractory tumors. 1 ongoing CR was observed in a refractory BRAF-mutated melanoma. A biologically active dose has been reached, although MTD has not been determined.
Clinical • P1 data
|
BRAF (B-raf proto-oncogene) • GSK3B (Glycogen Synthase Kinase 3 Beta)
|
BRAF V600E • BRAF mutation • BRAF V600 • BRAF V600K
|
carboplatin • gemcitabine • doxorubicin hydrochloride • Abraxane (albumin-bound paclitaxel) • irinotecan • lomustine • elraglusib (9-ING-41)
almost2years
Distinct Molecular Profiles and Immunotherapy Treatment Outcomes of V600E and V600K BRAF-Mutant Melanoma. (PubMed, Clin Cancer Res)
In patients treated with anti-PD-1, V600K (n = 19) had superior outcomes than V600E (n = 84), including response rate (53% vs. 29%, P = 0.059), PFS (median, 19 vs. 2.7 months, P = 0.049), and overall survival (20.4 vs. 11.7 months, P = 0.081).BRAF V600K melanomas appear to benefit less from BRAFi±MEKi than V600E, potentially due to less reliance on ERK pathway activation and greater use of alternative pathways. In contrast, these melanomas have higher mutational load and respond better to immunotherapy.
Clinical • Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • DUSP6 (Dual specificity phosphatase 6)
|
BRAF V600E • BRAF V600 • BRAF V600K
almost2years
Consistency and reproducibility of next-generation sequencing in cytopathology: A second worldwide ring trial study on improved cytological molecular reference specimens. (PubMed, Cancer Cytopathol)
The data show that the detection of low-abundance mutations is still clinically challenging and may require a visual inspection of sequencing reads to detect. Genomic reference standards in a cytocentrifuge/cytospin format are a valid tool for regular quality assessment of laboratories performing molecular studies on cytology with low-AF mutations.
Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • PSMD4 (Proteasome 26S Subunit Non-ATPase 4)
|
BRAF V600E • KRAS mutation • EGFR mutation • BRAF mutation • BRAF V600 • BRAF V600K
almost2years
BEAVER: Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations (clinicaltrials.gov)
P2, N=26, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting
Enrollment closed • Circulating tumor DNA
|
BRAF (B-raf proto-oncogene) • KIAA1549
|
BRAF V600E • BRAF mutation • BRAF V600K • BRAF fusion • BRAF V600R • BRAF V600M • BRAF T599 • BRAF V600D • BRAF V600_K601delinsE • BRAF K601
|
Mektovi (binimetinib) • Braftovi (encorafenib)
almost2years
Systemic adjuvant therapy for adult patients at high risk for recurrent cutaneous or mucosal melanoma: an Ontario Health (Cancer Care Ontario) clinical practice guideline. (PubMed, Curr Oncol)
For patients with completely resected cutaneous or mucosal melanoma with a high risk of recurrence, the recommended adjuvant therapies are nivolumab, pembrolizumab, or dabrafenib-trametinib for patients with BRAF V600E or V600K mutations; nivolumab or pembrolizumab are recommend for patients with BRAF wild-type disease. Use of ipilimumab is not recommended. Molecular testing should be conducted to help guide treatment decisions. Interferon alfa, chemotherapy regimens, vaccines, levamisole, bevacizumab, bacillus Calmette-Guérin, and isolated limb perfusion are not recommended for adjuvant treatment of cutaneous melanoma except as part of a clinical trial.
Clinical • Clinical guideline • Journal • PD(L)-1 Biomarker
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tafinlar (dabrafenib) • Yervoy (ipilimumab) • Intron A (interferon α-2b) • levamisole
almost2years
Testing of the Anti Cancer Drugs CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib) in Advanced Stage Non-small Cell Lung Cancer (clinicaltrials.gov)
P1, N=85, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Mar 2020 --> Jun 2020
Clinical • Trial initiation date
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
|
BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • BRAF V600K • KEAP1 mutation • NFE2L2 mutation
|
sapanisertib (CB-228) • telaglenastat (CB-839)
almost2years
Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor (clinicaltrials.gov)
P1, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2020 --> Dec 2020
Clinical • Enrollment closed • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Keytruda (pembrolizumab) • trebananib (AMG 386)
almost2years
[VIRTUAL] Clinical outcomes in patients with BRAFV600 mutant melanoma and undetectable circulating tumor DNA treated with dabrafenib and trametinib. (ASCO 2020)
The absence of detectable BRAFV600 ctDNA at baseline is associated with improved PFS and OS in patients receiving treatment with dabrafenib and trametinib. Research Funding: U.S. National Institutes of Health, Pharmaceutical/Biotech Company
Clinical • Clinical data
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mekinist (trametinib) • Tafinlar (dabrafenib)
almost2years
Acral Lentiginous Melanomas Harbour Intratumor Heterogeneity in BRAF Exon 15, With Mutations Distinct From V600E/V600K. (PubMed, Am J Dermatopathol)
Most (62.5%) of the missense BRAF exon 15 mutations found in the ALM samples examined here were deemed "detrimental" for protein function according to at least 2 functional prediction programs, and 3 mutations (37.5%) were predicted to be "neutral," with no effect on protein function. BRAF exon 15 mutations were detected frequently in ALM and displayed heterogeneity, a finding to be further investigated.
Journal
|
BRAF (B-raf proto-oncogene)
|
BRAF V600 • BRAF V600K • BRAF exon 15 mutation
almost2years
A Rare BRAF V600E mutation detected by Next Generation Sequencing in a superficial spreading melanoma: case report and potential diagnostic implications. (PubMed, J Eur Acad Dermatol Venereol)
According to the COSMIC database (Catalogue Of Somatic Mutations In Cancer, Apr 2019 [1]) 41% of the melanomas harbor BRAF oncogene mutations and approximately 97% of BRAF mutations are situated in codon 600. The most common mutation (80-90%) is represented by a substitution of valine to glutamic acid (V600E), followed by valine to lysine (V600K; 5-12%) [1].
Clinical • Journal
|
BRAF (B-raf proto-oncogene)
|
BRAF V600 • BRAF V600K
almost2years
Clinical • Trial primary completion date
|
BCL2 (B-cell CLL/lymphoma 2)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mekinist (trametinib) • Tafinlar (dabrafenib) • navitoclax (ABT 263)
almost2years
Clinical • Trial initiation date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib)
almost2years
Clinical • New P1 trial
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
|
BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • BRAF V600K • KEAP1 mutation • NFE2L2 mutation
|
sapanisertib (CB-228) • telaglenastat (CB-839)
almost2years
BECOME-MB: Stereotactic Radiosurgery Added to Binimetinib and Encorafenib in Patients With BRAFV600 Melanoma With Brain Metastasis (clinicaltrials.gov)
P2, N=150, Not yet recruiting, UNICANCER | Trial completion date: Sep 2026 --> Sep 2027 | Initiation date: Sep 2019 --> Sep 2020 | Trial primary completion date: Sep 2022 --> Sep 2023
Clinical • Trial completion date • Trial initiation date • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib)
2years
Pfizer PF-06688992 in Patients With Stage III or Stage IV Melanoma (clinicaltrials.gov)
P1, N=7, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: May 2020 --> Jan 2020 | Trial primary completion date: May 2020 --> Jan 2020
Clinical • Trial completion • Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
PF-06688992
2years
A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies (clinicaltrials.gov)
P1/2, N=570, Recruiting, Boston Biomedical, Inc | Trial primary completion date: Mar 2020 --> Dec 2020
Clinical • Trial primary completion date
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
BRAF V600E • HER-2 positive • BRAF V600 • HER-2 negative • ALK positive • BRAF V600K • ER negative • PGR negative
|
Abraxane (albumin-bound paclitaxel) • napabucasin (BBI608)
2years
Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors (clinicaltrials.gov)
P1, N=42, Recruiting, Array BioPharma | Trial completion date: Dec 2024 --> Aug 2022 | Trial primary completion date: Dec 2022 --> Aug 2021
Clinical • Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600K
|
Mektovi (binimetinib) • Braftovi (encorafenib) • modafinil • bupropion • dextromethorphan • losartan potassium • omeprazole • rosuvastatin
3years
Clinical • Enrollment change
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K • BRAF V600R • BRAF V600D
|
Zelboraf (vemurafenib)
3years
Clinical • New P2 trial
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Zelboraf (vemurafenib)
3years
MEK Inhibitor AZD6244 in Treating Patients With Stage III or Stage IV Melanoma (clinicaltrials.gov)
P2, N=40, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed
Clinical • Trial completion
|
BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
|
BRAF V600E • NRAS mutation • BRAF V600 • BRAF V600K
|
Koselugo (selumetinib)
3years
Clinical • New P3 trial
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Zelboraf (vemurafenib) • Mektovi (binimetinib) • Braftovi (encorafenib)
4years
Clinical • New P1 trial • IO biomarker
|
BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Xpovio (selinexor)
almost9years
Clinical • Trial termination
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Zelboraf (vemurafenib)
over9years
Clinical • Enrollment change
|
BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • BRAF V600K
|
Tafinlar (dabrafenib)