Zelboraf (vemurafenib) / Roche 
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 50 Diseases   65 Trials   65 Trials   4287 News 


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  • ||||||||||  Journal:  Resistance to MAPK inhibitors in melanoma involves activation of the IGF-1R-MEK5-Erk5 pathway. (Pubmed Central) -  Feb 9, 2020   
    The ERKi-resistant cells were also resistant to vemurafenib (VMF), trametinib (TMT), and combined treatment with either VMF and SCH or TMT and SCH...Inhibition of IGF1R with linsitinib blocked Erk5 activation in SCH-resistant cells and decreased their growth in 3D spheroid growth assays as well as in NOD scid gamma (NSG) mice...In addition, we found that the decreased Erk1/2 activation in SCH-resistant cells involved reduced expression and function of TGF-alpha. These data reveal an escape signaling route that melanoma cells use to bypass Erk1/2 blockade during targeted melanoma treatment and offer several possible targets whose disruption may circumvent resistance.
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Journal:  Cell-free DNA BRAF V600E measurements during BRAF inhibitor therapy of metastatic melanoma: long-term analysis. (Pubmed Central) -  Feb 8, 2020   
    We assessed the status of the BRAF V600E mutation in cell-free circulating tumor DNA (cfDNA) isolated from the plasma of patients with metastatic melanoma treated with the BRAF inhibitor vemurafenib, collected at different time points during therapy to evaluate the sensitivity and specificity of quantitative polymerase chain reaction and droplet digital polymerase chain reaction (ddPCR) and the correlation between the level of plasma cfDNA p.V600E and the long-term clinical outcome...Monitoring of plasma BRAF p.V600E cfDNA concentrations in patients with metastatic melanoma on targeted therapy may have prognostic value. Undetectable cfDNA p.V600E before and during treatment was associated with a favorable prognosis.
  • ||||||||||  Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
    Retrospective data, Journal, Adverse events:  Effect of early adverse events on response and survival outcomes of advanced melanoma patients treated with vemurafenib or vemurafenib plus cobimetinib: A pooled analysis of clinical trial data. (Pubmed Central) -  Feb 7, 2020   
    Adverse events requiring vemurafenib/cobimetinib dose adjustment within the first 28 days of therapy were significantly associated with OS (Hazard Ratio (HR) [95%CI]: Dose reduced/interrupted = 0.79 [0.65-0.96]; Drug withdrawn = 1.18 [0.71-1.96]; P = 0.032), PFS (HR [95%CI]: Dose reduced/interrupted = 0.82 [0.67-0.99]; Drug withdrawn = 1.58 [0.97-2.58]; P = 0.017) and objective response (Odds Ratio (OR) [95%CI]: Dose reduced/interrupted = 1.35 [0.99-1.85]; Drug withdrawn = 0.17 [0.06-0.43]; P = <0.001). Arthralgia occurring within the first 28 days of vemurafenib or vemurafenib plus cobimetinib therapy was also significantly associated with favourable OS (P = 0.026), PFS (P = 0.042) and objective response (P = 0.047).
  • ||||||||||  buparlisib (BKM120) / Novartis, Adlai Nortye, Zelboraf (vemurafenib) / Roche
    Journal:  A dual pathway inhibition strategy using BKM120 combined with vemurafenib is poorly tolerated in BRAF V600 mutant advanced melanoma. (Pubmed Central) -  Feb 7, 2020   
    Aberrant signaling in the PI3K pathway has been implicated in both melanoma oncogenesis and in BRAF inhibitor resistance (e. g. Dankort et al., 2009; Goel et al., 2006). PTEN loss, which leads to increased PI3K activity, is common in patients treated with the BRAF inhibitor vemurafenib (McArthur et al., 2011) and decreased PTEN expression has been identified as a predictor of decreased PFS in patients treated with the drug (Nathanson et al., 2013).
  • ||||||||||  Review, Journal, IO Biomarker:  Targeting BRAF mutations in non-small cell lung cancer. (Pubmed Central) -  Feb 6, 2020   
    A 2-cohort phase 2 study demonstrated an ORR of 33% vs. 67% and PFS of 5.5 vs. 10.2 months in those treated with single agent dabrafenib vs. dabrafenib and trametinib respectively...BRAF mutated NSCLC treated with chemotherapy have been widely reported to be associated with worse outcomes when compared to those without a mutation. With efficacy of combination BRAF/MEK established and early evidence of immune checkpoint inhibitor activity careful consideration should be given when choosing the most appropriate therapy in this select patient cohort.
  • ||||||||||  Opdivo (nivolumab) / BMS, Braftovi (encorafenib) / Pfizer, Mektovi (binimetinib) / Pfizer
    Trial completion date, Trial primary completion date:  Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma (clinicaltrials.gov) -  Feb 6, 2020   
    P1,  N=20, Recruiting, 
    With efficacy of combination BRAF/MEK established and early evidence of immune checkpoint inhibitor activity careful consideration should be given when choosing the most appropriate therapy in this select patient cohort. Trial completion date: Sep 2021 --> Sep 2022 | Trial primary completion date: Sep 2020 --> Sep 2021
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Journal:  YY1 cooperates with TFEB to regulate autophagy and lysosomal biogenesis in melanoma. (Pubmed Central) -  Jan 27, 2020   
    Moreover, suppression of YY1 enhanced the antitumor efficiency of vemurafenib both in vitro and in vivo. Collectively, these studies identify YY1 as a novel cotranscription factor of TFEB in regulating autophagy and lysosomal functions and suggest YY1 could be a therapeutic target in cancer treatment.
  • ||||||||||  Torisel (temsirolimus) / Pfizer, Zelboraf (vemurafenib) / Roche
    Enrollment change, Trial primary completion date, Combination therapy, Metastases:  Vemurafenib in Combination With Everolimus or Temsirolimus With Advanced Cancer (clinicaltrials.gov) -  Jan 23, 2020   
    P1,  N=27, Active, not recruiting, 
    The reasons for choosing between TT and IO, or substances within the groups, were different. N=114 --> 27 | Trial primary completion date: Dec 2019 --> Dec 2020
  • ||||||||||  Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
    Journal:  Decreased photosensitivity to UVA on vemurafenib combined with cobimetinib. (Pubmed Central) -  Jan 17, 2020   
    Dummer et al. and our team have previously shown that this photosensitivity was exclusively induced by UVA and defined by a minimum erythema dose (MED) of UVA of less than 20 joules, present in about 84% of patients and disappearing rapidly upon treatment discontinuation.
  • ||||||||||  Zelboraf (vemurafenib) / Roche, XL888 / Exelixis, Merck (MSD)
    Trial completion date:  Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma (clinicaltrials.gov) -  Jan 13, 2020   
    P1,  N=21, Active, not recruiting, 
    and our team have previously shown that this photosensitivity was exclusively induced by UVA and defined by a minimum erythema dose (MED) of UVA of less than 20 joules, present in about 84% of patients and disappearing rapidly upon treatment discontinuation. Trial completion date: Dec 2019 --> Apr 2020
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Journal:  VCAM-1 Upregulation Contributes to Insensitivity of Vemurafenib in BRAF-Mutant Thyroid Cancer. (Pubmed Central) -  Jan 10, 2020   
    The present study is the first to demonstrate that VCAM-1 is upregulated in thyroid cancer cells treated with vemurafenib and contributes to vemurafenib resistance in BRAF-mutant thyroid cancer cells. Targeting the PI3K-Akt-mTOR pathway-mediated VCAM-1 response may be an alternative strategy to sensitize BRAF-mutant thyroid cancers to vemurafenib.