- |||||||||| Zelboraf (vemurafenib) / Roche
Journal, Monotherapy: Long Term Outcomes in Patients with Relapsed or Refractory Hairy Cell Leukemia Treated with Vemurafenib Monotherapy. (Pubmed Central) - Aug 6, 2022
P2
With a median follow-up duration of 11.7 months, we observed relapses in 29% of the patients but the long-term clinical outcome and response or acquired resistance to vemurafenib retreatment have not been previously reported. Herein, we report the long-term follow-up data of the entire patient cohort in the completed U.S. clinical trial (NCT01711632) including the ORR, relapse free survival, clinical factors associated with improved survival as well as outcomes after retreatment with vemurafenib or alternative agents.
- |||||||||| Zelboraf (vemurafenib) / Roche
Trial completion, Trial completion date, Trial primary completion date: Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E (BRAFV600E)-Mutant Gliomas (clinicaltrials.gov) - Aug 3, 2022
P1, N=40, Completed,
Conclusions Our study points to a possible effect of ICI based combination therapies on the gut microbiota and provides implications for the treatment of advanced melanoma patients. Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Feb 2022 | Trial primary completion date: Jun 2022 --> Feb 2022
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Targeting of the Lipid Metabolism Impairs Resistance to BRAF Kinase Inhibitor in Melanoma. (Pubmed Central) - Aug 2, 2022
The aim of the present study was to explore the involvement of lipid metabolism in melanoma resistance and assess the effects of its targeting in cellular models of melanoma with acquired resistance to the BRAF-inhibitor PLX4032/Vemurafenib...Overall, our findings reveal that lipid metabolism affects melanoma sensitivity to BRAF inhibitors and that extracellular lipid availability may influence tumor cell response to treatment, a relevant finding in the frame of personalized therapy. In addition, our results indicate new candidate targets for drug combination treatments.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Analysis of Alternative mRNA Splicing in Vemurafenib-Resistant Melanoma Cells. (Pubmed Central) - Jul 29, 2022
Interestingly, they identified AS caused alterations in the expression of melanin synthesis and cell migration genes in the vemurafenib-resistant cells. This analysis shows that combining different AS analysis approaches produces reliable results and meaningful, biologically testable hypotheses.
- |||||||||| LY3022855 / Eli Lilly
Trial primary completion date: LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma (clinicaltrials.gov) - Jul 28, 2022
P1/2, N=5, Active, not recruiting,
The observed risk reduction for CNS mets is consistent with the overall benefit observed for A+V+C in the IMspire150 study. Trial primary completion date: Jun 2022 --> Dec 2022
- |||||||||| 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) - Jul 28, 2022
P1, N=20, Recruiting,
Trial primary completion date: Jun 2022 --> Dec 2022 Trial completion date: Sep 2022 --> Dec 2022 | Trial primary completion date: Sep 2022 --> Dec 2022
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Implementing a Scoring Function Based on Interaction Fingerprint for Autogrow4: Protein Kinase CK1δ as a Case Study. (Pubmed Central) - Jul 27, 2022
A class of targets that have proven to be particularly suitable for this method is represented by kinases, as demonstrated by the approval of BRAF inhibitor vemurafenib...In the current work, we present and discuss a modified version of the Autogrow code that implements a custom scoring function based on the similarity between the interaction fingerprint of investigated compounds and a crystal reference. To validate its performance, we performed both a de novo and a lead-optimization run (as described in the original publication), evaluating the ability of our fingerprint-based protocol to generate compounds similar to known CK1δ inhibitors based on both the predicted binding mode and the electrostatic and shape similarity in comparison with the standard Autogrow protocol.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Zelboraf (vemurafenib) / Roche, Yervoy (ipilimumab) / Ono Pharma, BMS
Review, Journal: Metastatic malignant melanoma of the breast: report of a case and review of the literature. (Pubmed Central) - Jul 23, 2022
Nevertheless, breast metastases must be suspected in patients with a history of malignant melanoma. Moreover, recent breakthroughs in the Braf and MEK inhibitors and immune checkpoint inhibition therapies have impressively improved prognosis in patients affected by melanoma.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Zelboraf (vemurafenib) / Roche, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
P3 data, Journal, IO biomarker: COLUMBUS 5-Year Update: A Randomized, Open-Label, Phase III Trial of Encorafenib Plus Binimetinib Versus Vemurafenib or Encorafenib in Patients With BRAF V600-Mutant Melanoma. (Pubmed Central) - Jul 22, 2022
P3
No abstract available In this 5-year update of part 1 of the COLUMBUS trial, encorafenib plus binimetinib treatment demonstrated continued long-term benefits and a consistent safety profile in patients with BRAF V600-mutant melanoma.
- |||||||||| Zelboraf (vemurafenib) / Roche
Biomarker, Enrollment change, Trial completion date, Metastases: Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial) (clinicaltrials.gov) - Jul 18, 2022
P2, N=4, Active, not recruiting,
Nevertheless, the drug seems to be a good option for second-line treatment for patients with ECD and BRAFV600 mutation. N=49 --> 4 | Trial completion date: Jun 2022 --> Jul 2023
- |||||||||| Mekinist (trametinib) / Novartis, Tafinlar (dabrafenib) / Novartis, Zelboraf (vemurafenib) / Roche
INFANT LOW-GRADE GLIOMAS: MOLECULAR CHARACTERISTICS AND RESULTS OF TARGETED THERAPY (Hall 7) - Jul 16, 2022 - Abstract #SIOP2022SIOP_484;
One patient with BRAF V600E died of disease 3 months after the end of vemurafenib; another patient with BRAF V600E has SD on combine BRAF- and MEK inhibitors therapy. All children with DIGs are presented in complete remission after surgery.ConclusionsTargeted therapy may be an effective treatment option, but it is at times restricted by toxicity and development of resistance.
- |||||||||| Trial completion date, Trial initiation date, Trial primary completion date: SMMART Adaptive Clinical Treatment (ACT) Trial (clinicaltrials.gov) - Jul 14, 2022
P2, N=131, Not yet recruiting,
These potential repurposed drugs may prove useful in antiviral drug development against HCV. Trial completion date: Mar 2025 --> Mar 2026 | Initiation date: Apr 2022 --> Dec 2022 | Trial primary completion date: Mar 2025 --> Mar 2026
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Encoding BRAF inhibitor functions in protein degraders. (Pubmed Central) - Jul 12, 2022
First-generation BRAF inhibitors could lead to paradoxical activation of the MAPK pathway, limiting their clinical usefulness. Here, we show the development of two series of BRAF-targeting PROTACs and demonstrate that the exchange of the inhibitor scaffold from vemurafenib to paradox-breaker ligands resulted in BRAF degraders that did not cause paradoxical ERK activation.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal, PD(L)-1 Biomarker, IO biomarker: Combination of a STAT3 inhibitor with anti-PD-1 immunotherapy is an effective treatment regimen for a vemurafenib-resistant melanoma. (Pubmed Central) - Jul 6, 2022
Moreover, combination therapy with APT-9R and an anti-PD-1 antibody enhanced significant suppression of tumor growth by decreasing infiltration of these immunosuppressive immune cells while increasing the infiltration and cytotoxicity of CD8 T cells. These findings suggest that combined blockade of STAT3 and PD-1 signaling pathways may be an effective treatment option for overcoming poor therapeutic outcomes associated with drug-resistant BRAF-mutant melanoma.
- |||||||||| Retrospective data, Journal: BRAF-MEK inhibitor therapy in melanoma (Pubmed Central) - Jun 28, 2022
Each combination displayed a slightly different safety profile. In our retrospective analysis both BRAF-MEK inhibitor combination therapies showed favorable efficacy with a slightly different spectrum of toxicity profile.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Journal, Combination therapy: Encorafenib and Binimetinib Combination Therapy in Metastatic Melanoma. (Pubmed Central) - Jun 28, 2022
These approvals were based on findings from the COLUMBUS trial, which demonstrated improvement in progression-free survival and overall survival with the combination of encorafenib plus binimetinib compared with vemurafenib alone. Encorafenib plus binimetinib is the third BRAF plus MEK inhibitor combination to be approved, and there are clinical and practical differences between the combination regimens that should be considered when selecting an appropriate treatment regimen for patients.
- |||||||||| Zelboraf (vemurafenib) / Roche
Overexpression of ezrin is associated with acquired resistance to vemurafenib in BRAFV600E mutated colon cancer cells (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_1032;
In addition, mRNA expression analysis of colorectal adenocarcinoma in the TCGA dataset using cBioPortal revealed higher expression of EZR in BRAFV600E mutated CRC in comparison with unaltered group. Conclusion Up-regulation of ezrin is a specific molecular feature of vemurafenib-resistant BRAFV600E mutated colon cancer cells whose pharmacological targeting could provide an opportunity to reverse vemurafenib resistance.
- |||||||||| Zelboraf (vemurafenib) / Roche
Can extracellular vesicles transmit vemurafenib resistance in melanoma cells in vitro? (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_770;
If treated in combination, EVs attenuated the antitumor effect of vemurafenib in a cell line dependent manner. Conclusion Thus our results may indicate that extracellular vesicles can prevent vemurafenib cells and they might be a mechanism by which resistance against the BRAF inhibitor vemurafenib emerges.
- |||||||||| Zelboraf (vemurafenib) / Roche
New insights on melanoma treatment: how can seriniquinones benefit? (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_541;
This work aims to elucidate the role of autophagy in the cytotoxicity of serinoquinones and the susceptibility of vemurafenib-resistant cells to these compounds...After treatments with bafilomycin A1 (autophagy inhibitor), rapamycin (autophagy inducer), Z-VAD-FMK (apoptosis inhibitor) or doxorubicin (apoptosis inducer), cells were submitted to MTT assay to determinate the respective IC 50 (half maximal inhibitory concentration) and to Western blotting analyses to evaluate key-protein expressions from autophagy and apoptosis pathways...Conclusion Due to its novel mechanism of action, seriniquinones have a great potential not only to inaugurate a new anticancer drug class but also to become a pharmacological tool to understand the role of dermcidin in the context of carcinogenesis and chemoresistance. This way, more studies are necessary and dermcidin silencing may bring new insights on this relationship.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche, Zelboraf (vemurafenib) / Roche
Melanosphere culture of BRAF mutant melanoma identifies CD20 as an adjuvant therapeutic target () - Jun 23, 2022 - Abstract #BAD2022BAD_702;
Combined vemurafenib; rituximab anti-CD20 antibody treatment doubled the killing of BRAF mutant MM cells. Hence, rituximab augments the efficacy of BRAF inhibitor therapy in the subgroup of BRAF mutant MM that harbours a CD20+ subpopulation.
- |||||||||| Journal: Epidermal necrolysis in the context of immuno-oncologic medication as well as kinase inhibitors and biologics. (Pubmed Central) - Jun 22, 2022
Fourteen cases were EN-like reactions: six bullous lichenoid drug eruptions (DE) to pembrolizumab (2), obinutuzumab, nivolumab, rituximab, infliximab/nivolumab, and eight multiforme-like DE to rituximab (2), adalimumab, ramucirumab, bevacizumab, vemurafenib, sorafenib (2)...A correct diagnosis is highly relevant in terms of prognosis and use of these drugs in malignoma treatment. Re-exposure is contraindicated in EN, but possible in other DE after rigorous risk-benefit evaluation.
- |||||||||| Review, Journal: Targeted therapies in the medical management of craniopharyngioma. (Pubmed Central) - Jun 9, 2022
A preliminary report of a recent phase II clinical trial has shown a therapeutic response in 93.7% of patients with BRAF -mutated PCP, with an 85% reduction in tumor size. In the present review we comment on the efficacy and safety of the different drugs being used in patients with PCP.
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