- |||||||||| Mekinist (trametinib) / Novartis, Opdivo (nivolumab) / Ono Pharma, BMS, Tafinlar (dabrafenib) / Novartis
[VIRTUAL] Comparative Efficacy of Combination of Dabrafenib and Trametinib Against Other Adjuvant Therapies for Melanoma () - Apr 12, 2021 - Abstract #ISPOR2021ISPOR_385;
The results were found to be comparable for RFS between dabrafenib plus trametinib and immune-checkpoint inhibitors i.e. nivolumab (HR: 0.95 [95% CI: 0.70, 1.29) and pembrolizumab (HR: 0.86 [95% CI: 0.67, 1.12). CONCLUSIONS : The NMA findings showed that dabrafenib plus trametinib has improved efficacy over treatment options such as ipilimumab, interferons and chemotherapy and comparable efficacy with immune-checkpoint inhibitors in the adjuvant setting.
- |||||||||| Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Journal, IO biomarker: The discovery and development of binimetinib for the treatment of melanoma. (Pubmed Central) - Apr 10, 2021
Treatment approaches to patients with BRAF-mutated metastatic melanoma should be individualized and binimetinib in combination with encorafenib is a reasonable oral strategy with a reasonably tolerated toxicity profile. The cost of treatment and durability of response should be incorporated into the discussion as part of the overall medical decision-making.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Loss of Spry1 reduces growth of BRAF-mutant cutaneous melanoma and improves response to targeted therapy. (Pubmed Central) - Apr 10, 2021
Disruption of this feedback loop rendered Spry1 cells more susceptible to apoptosis and markedly improved response to BRAFi both in vitro and in vivo, as a consequence of the detrimental effect of ERK1/2 hyperactivation observed upon Spry1 abrogation. Therefore, targeting Spry1 might offer a treatment strategy for BRAF-mutant CM by inducing the toxic effects of ERK-mediated signaling.
- |||||||||| Tafinlar (dabrafenib) / Novartis, Zelboraf (vemurafenib) / Roche
[VIRTUAL] CRISPR-Cas9 Engineered Isogenic Luciferase-expressing Cell Lines as In Vitro and In Vivo Models for Cancer Research (Channel 3) - Apr 10, 2021 - Abstract #EACR2021EACR_200;
Results and Discussions Both A375-Luc2 and KRASG13D A375-Luc2 grew as subcutaneous tumors with increasing levels of bioluminescence when injected into nude mice. In addition, a portfolio of 5 human isogenic luciferase reporter cell line pairs and 18 human and mouse luciferase reporter cell lines were developed for the study of various cancer types Conclusion In conclusion, the combination of two technologies CRISPR-Cas9 technology and stable luciferase expression allows for the generation of isogenic luciferase-expressing cell lines, which are valuable tools for elucidating mechanisms involved in tumorigenesis and for studying drug responses in vitro and in vivo.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date, Surgery: RadioCoBRIM: Vemurafenib Plus Cobimetinib After Radiosurgery in Patients With BRAF-mutant Melanoma Brain Metastases (clinicaltrials.gov) - Apr 9, 2021
P2, N=20, Active, not recruiting,
In addition, a portfolio of 5 human isogenic luciferase reporter cell line pairs and 18 human and mouse luciferase reporter cell lines were developed for the study of various cancer types Conclusion In conclusion, the combination of two technologies CRISPR-Cas9 technology and stable luciferase expression allows for the generation of isogenic luciferase-expressing cell lines, which are valuable tools for elucidating mechanisms involved in tumorigenesis and for studying drug responses in vitro and in vivo. Recruiting --> Active, not recruiting | N=32 --> 20 | Trial completion date: Jul 2022 --> Dec 2022 | Trial primary completion date: Jul 2022 --> Dec 2022
- |||||||||| Opdivo (nivolumab) / BMS, Braftovi (encorafenib) / Pfizer, Mektovi (binimetinib) / Pfizer
Enrollment open: Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma (clinicaltrials.gov) - Apr 5, 2021
P1, N=20, Recruiting,
Recruiting --> Active, not recruiting | N=32 --> 20 | Trial completion date: Jul 2022 --> Dec 2022 | Trial primary completion date: Jul 2022 --> Dec 2022 Suspended --> Recruiting
- |||||||||| Zelboraf (vemurafenib) / Roche
Clinical, Journal: The 487th case: prominent eyes, headache, blurred vision (Pubmed Central) - Apr 2, 2021
The patient's condition is stable and still in follow-up. Although ECD is a rare histiocytosis, clinicians should pay attention to its manifestations and differential diagnoses.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: USP22 promotes melanoma and BRAF inhibitor resistance via YAP stabilization. (Pubmed Central) - Mar 30, 2021
Furthermore, overexpression of USP22 conferred vemurafenib resistance in a YAP-dependent manner. Overall, the present study revealed the important role of the USP22/YAP axis in melanoma and BRAF inhibitor resistance, and provides a rationale to target USP22/YAP for melanoma treatment.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche, Tecentriq (atezolizumab) / Roche
[VIRTUAL] A Surgeon Assessment Tool to Evaluate Baseline and Post-Neoadjuvant Operability in a Melanoma Clinical Trial () - Mar 26, 2021 - Abstract #SSO2021SSO_13;
P2
These data support use of a surgeon assessment tool to improve understanding of the effect of NST on the technical conduct of operation for stage III melanoma. Validation of these findings across other prospective trials and further study to investigate associations with morbidity and patient-reported outcomes are warranted.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS
Journal, PD(L)-1 Biomarker: Systemic Therapy for Melanoma: ASCO Guideline. (Pubmed Central) - Mar 26, 2021
No recommendation could be made for or against specific therapy for uveal melanoma. Additional information is available at www.asco.org/melanoma-guidelines.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Zastosowanie wemurafenibu w opornej na leczenie histiocytozie z komórek langerhansa. (Pubmed Central) - Mar 23, 2021
In this paper we present a girl with severe Langerhans Cell Histiocytosis, not responding to conventional treatment, who only after adding vemurafenib achieved a regression of symptoms. This case shows the necessity to expand the diagnostics with molecular tests and the possibility of applying targeted treatment for patients of this kind.
- |||||||||| Zelboraf (vemurafenib) / Roche
Preclinical, Journal: Selective inhibition of V600E-mutant BRAF gene induces apoptosis in thyroid carcinoma cell lines. (Pubmed Central) - Mar 23, 2021
We investigated how a selective inhibitor of BRAF PLX4032 affects the proliferation and inflammatory cytokine levels of thyroid cancer...In the 8505C cells, inflammatory cytokines such as IL-8 and MMP-3 were down-regulated. These findings suggest the possibility that the BRAF mutation needs to target inflammatory signaling pathways in the treatment of thyroid cancer.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche, Tecentriq (atezolizumab) / Roche
Trial completion date, Trial primary completion date, IO biomarker, Metastases: ImmunoCobiVem: Evaluating the Efficacy and Safety of a Sequencing Schedule of Cobimetinib Plus Vemurafenib Followed by Immunotherapy With an Anti- PD-L1 Antibody in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma (clinicaltrials.gov) - Mar 22, 2021
P2, N=176, Active, not recruiting,
These findings suggest the possibility that the BRAF mutation needs to target inflammatory signaling pathways in the treatment of thyroid cancer. Trial completion date: Jun 2022 --> Jun 2024 | Trial primary completion date: Mar 2022 --> Mar 2024
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: LGR5 epithelial tumor stem-like cells generate a 3D-organoid model for ameloblastoma. (Pubmed Central) - Mar 19, 2021
Treatment with a selective BRAF inhibitor, vemurafenib, unexpectedly enriched the subpopulation of LGR5 AM-EpiSCs in tumor 3D organoids, which may have explained therapeutic resistances and recurrences. These findings suggest that LGR5 AM-EpiSCs play a pivotal role in pathogenesis and progression of AM and targeted inhibition of both BRAF and LGR5 potentially serves a novel nonsurgical adjuvant therapeutic approach for this aggressively benign jaw tumor.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Mutant-selective degradation by BRAF-targeting PROTACs. (Pubmed Central) - Mar 19, 2021
Using vemurafenib-based PROTACs, we achieve low nanomolar degradation of all classes of BRAF mutants, but spare degradation of WT RAF family members...Mechanistic studies reveal that BRAF is spared due to weak ternary complex formation in cells owing to its quiescent inactivated conformation, and activation of BRAF sensitizes it to degradation. This study highlights the degree of selectivity achievable with degradation-based approaches by targeting mutant BRAF-driven cancers while sparing BRAF, providing an anti-tumor drug modality that expands the therapeutic window.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Gazyva (obinutuzumab) / Roche, Biogen, Zelboraf (vemurafenib) / Roche
New P2 trial: STEP-WISE COMBINATION OF OBINUTUZUMAB, VEMURAFENIB AND COBIMETINIB IN PATIENTS WITH HAIRY CELL LEUKEMIA (HCL) PREVIOUSLY TREATED WITH PURINE ANALOGS OR UNFIT FOR CHEMOTHERAPY: A PHASE-2, SINGLE-ARMS, ITALIAN, MULTICENTER STUDY (HCL-PG04) COMBINAZIONE SEQUENZIALE DI OBINUTUZUMAB, VEMURAFENIB E COBIMETINIB IN PAZIENTI CON LEUCEMIA A CELLULE CAPELLUTE (HAIRY CELL LEUKEMIA (EUDRACT) - Mar 18, 2021
P2, N=42, Ongoing,
- |||||||||| Zelboraf (vemurafenib) / Roche
Preclinical, Journal: Role of VEGFR-1 in melanoma acquired resistance to the BRAF inhibitor vemurafenib. (Pubmed Central) - Mar 18, 2021
These data suggest that VEGFR-1 up-regulation might contribute to melanoma progression and spreading after acquisition of a drug-resistant phenotype. Thus, VEGFR-1 inhibition with D16F7 mAb might be a suitable adjunct therapy for VEGFR-1 positive tumours with acquired resistance to vemurafenib.
- |||||||||| Zelboraf (vemurafenib) / Roche
[VIRTUAL] PD-L1 is an independent prognostic marker in Middle Eastern PTC and its expression is upregulated byBRAFV600E mutation () - Mar 13, 2021 - Abstract #AACR2021AACR_4211;
His case demonstrated that meaningful clinical responses can be achieved with sequential targeted therapy/immunotherapy in BRAF-mutated metastatic melanoma and the novel PD-1 antibody Sintilimab is worth further investigation for its efficacy in metastatic melanoma. Our data suggests that PD-L1 might represent a useful prognostic marker in Middle Eastern PTC and PD-L1 inhibition could be a potential therapeutic option for aggressive PTC cancers, such as tall cell variant, BRAF mutation positive patients that are unresponsive to standard treatment.
- |||||||||| Zelboraf (vemurafenib) / Roche
[VIRTUAL] HDAC8 activity regulates stress induced phenotype switching in melanoma () - Mar 11, 2021 - Abstract #AACR2021AACR_3719;
HDAC8 associated with EP300 and mediated the switch to an invasive, stress resistant state in melanoma cells by suppressing MITF and increasing c-Jun driven transcriptional programs. Targeting HDAC8 could be a strategy to limit plasticity in advanced melanoma, increasing the efficacy of current therapies.
- |||||||||| birinapant (TL 32711) / Medivir, Zelboraf (vemurafenib) / Roche
[VIRTUAL] Targeting SOX10-deficient cells to reduce resistance to targeted therapy in melanoma (Channel 05) - Mar 11, 2021 - Abstract #AACR2021AACR_2917;
Our preliminary data suggest that birinapant can delay or prevent resistance to BRAFi/MEKi in vivo. Together, these data suggest that SOX10 mediates phenotypic switching in cutaneous melanoma and enables tumor adaptation to altered microenvironments and drug treatments which could be targeted using cIAP1/2 inhibitors.
- |||||||||| Zelboraf (vemurafenib) / Roche
[VIRTUAL] Novel immune targets in melanoma by profiling of co-activators and co-receptors () - Mar 11, 2021 - Abstract #AACR2021AACR_2764;
Interestingly, treatment of MEL-2, MEL-V, KFM and GLM-2, our BRAFV600E containing patient-derived cells, with BRAFV600E inhibitor PLX4032 led to the upregulation of these molecules...We conclude that the BTLA-HVEM axis is a significant novel target in melanoma that can be used in combinatorial therapy with small molecule inhibitors of cell survival. Our results advocate the need for profiling of immune modulators on tumor cells prior to immunotherapy.
- |||||||||| indoximod (NLG8189) / Lumos Pharma, Zelboraf (vemurafenib) / Roche
[VIRTUAL] The indoleamine 2,3 dioxygenase-1 pathway drives intratumoral B cell maintenance () - Mar 11, 2021 - Abstract #AACR2021AACR_164;
Surprisingly, we found that D-1MT enhanced anti-tumor effects of the BRAF inhibitor, vemurafenib, in a preclinical model of BRAF mutant melanoma, suggesting that targeting B cells in this setting may be beneficial. Together, our data reveal a novel paradigm for the IDO1 pathway in regulating TIL-B cells, and uncovered IDO1 as a potential targetable mechanism of resistance to BRAF inhibition in melanoma.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Targeting PSMD14 inhibits melanoma growth through SMAD3 stabilization. (Pubmed Central) - Mar 10, 2021
Although melanoma therapy is improved by novel molecular targeted reagents, including vemurafenib, aberrant proliferation and early metastasis remain obstacles for melanoma; therefore, novel target molecules for melanoma need to be identified...Furthermore, SMAD3 expression increased in nucleus and SMAD3 degradation was delayed after PSMD14 knockdown. Thus, our present study suggests that targeting PSMD14 can inhibit melanoma growth and migration through either SMAD3 accumulation or SLUG reduction, respectively.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Icariside II overcomes BRAF inhibitor resistance in melanoma by inducing ROS production and inhibiting MITF. (Pubmed Central) - Mar 9, 2021
In the present study, we determined by MTT, flow cytometry and western blotting, respectively that IS potentiated the PLX4032‑induced downregulation of cell viability and increase in apoptosis and autophagy in BRAF inhibitor‑resistant melanoma...Furthermore, c‑Met is a direct transcriptional target of MITF in melanocytes and melanoma cells. It was also revealed that IS markedly inhibited MITF and c‑Met expression partially by increasing ROS production in BRAF inhibitor‑resistant melanoma cells.
- |||||||||| cladribine / Generic mfg.
Review, Journal: Skin changes in hairy cell leukemia. (Pubmed Central) - Mar 6, 2021
Publications from January 1980 to September 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS
Review, Journal, PD(L)-1 Biomarker, IO biomarker: Overcoming Immune Evasion in Melanoma. (Pubmed Central) - Mar 5, 2021
The proposed mechanism of action and the roles of immunotherapeutic agents, ipilimumab, nivolumab, pembrolizumab, and atezolizumab, adoptive T- cell therapy plus T-VEC in the treatment of advanced melanoma are discussed. In this review, we implore that a better understanding of the steps that mediate melanoma onset and progression, immune evasion strategies exploited by these tumor cells, and the identification of biomarkers to predict treatment response are critical in the design of improved strategies to improve clinical outcomes for patients with this deadly disease.
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