- |||||||||| tunlametinib (HL-085) / Tianjin Binjiang Pharma
Enrollment open, Metastases: Study of HL-085 and Vemurafinib in Metastatic Colorectal Cancer (mCRC) (clinicaltrials.gov) - May 31, 2023
P2, N=186, Recruiting,
Trial completion date: Aug 2022 --> Dec 2023 | Trial primary completion date: Aug 2022 --> Dec 2023 Not yet recruiting --> Recruiting
- |||||||||| Zelboraf (vemurafenib) / Roche
Neurodegenerative Langerhans cell histiocytosis presenting as a mimic of Leukodystrophy (Foyer 3B, 3rd Floor) - May 29, 2023 - Abstract #EPNS2023EPNS_897;
LCH-ND is a rare presentation of LCH with a neurodegenerative syndrome and a specific leukoencephalopathy-like pattern and can present without systemic involvement. ND-LCH should be in kept in mind in the differential diagnosis of CNS demyelination mimics, as prompt diagnosis and treatment is crucial.
- |||||||||| LY3022855 / Eli Lilly
P1/2 data, Journal, IO biomarker: A phase I/II study of LY3022855 with BRAF/MEK inhibition in patients with Melanoma. (Pubmed Central) - May 29, 2023
CSF1R inhibition with LY3022855 in combination with BRAF/MEK inhibition with vemurafenib and cobimetinib was difficult to tolerate in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration.
- |||||||||| Tafinlar (dabrafenib) / Novartis, Zelboraf (vemurafenib) / Roche
Journal: Targeting the BRAF pathway in haematological diseases. (Pubmed Central) - May 28, 2023
Physician familiarity is essential for the effective use of these agents. We review the Australian experience of BRAF/MEK inhibitor therapy in these rare haematological cancers.
- |||||||||| Opdivo (nivolumab) / BMS, Braftovi (encorafenib) / Pfizer, Mektovi (binimetinib) / Pfizer
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date: Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma (clinicaltrials.gov) - May 25, 2023
P1, N=13, Active, not recruiting,
The newly developed method demonstrated linearity for the detected drug concentration in the range of 20 to 2000 Recruiting --> Active, not recruiting | N=10 --> 13 | Trial completion date: Dec 2023 --> May 2028 | Trial primary completion date: Dec 2023 --> May 2028
- |||||||||| Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial (clinicaltrials.gov) - May 22, 2023
P1, N=2, Active, not recruiting,
This trial is registered at www.clinicaltrials.gov as NCT03585686. Recruiting --> Active, not recruiting | N=40 --> 2 | Trial completion date: Feb 2026 --> Jun 2027 | Trial primary completion date: Feb 2023 --> Jun 2025
- |||||||||| Recentin (cediranib) / AstraZeneca, dacarbazine / Generic mfg., Zelboraf (vemurafenib) / Roche
Journal, Metastases: Vitamin D Modulates the Response of Patient-Derived Metastatic Melanoma Cells to Anticancer Drugs. (Pubmed Central) - May 17, 2023
Our earlier studies documented that 1,25(OH)D and its low-calcaemic analogues potentiate the effectiveness of dacarbazine and cediranib, a pan-VEGFR inhibitor...Thus, patient-derived cells were preconditioned with 1,25(OH)D and treated with cediranib or vemurafenib, a BRAF inhibitor, depending on the BRAF mutation status of the patients enrolled in the study...Interestingly, regardless of the strict selection, cancer-derived fibroblasts (CAFs) became the major fraction of cultured cells over time, suggesting that melanoma growth is dependent on CAFs. In conclusion, the results of our study strongly emphasise that the active form of vitamin D, 1,25(OH)D, might be considered as an adjuvant agent in the treatment of malignant melanoma.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal, Cancer stem, Metastases: Reactive Oxygen Species Regulation of Chemoresistance and Metastatic Capacity of Melanoma: Role of the Cancer Stem Cell Marker CD271. (Pubmed Central) - May 16, 2023
Concordantly, resistance to the selective inhibitor of oncogenic BRAFV600E/K, vemurafenib, is mediated by the increased expression of CD271...DPI treatment affected the expression of CD271 and the ERK and Akt signaling pathways, leading to a drop in epithelial-mesenchymal transition (EMT), which undoubtedly promotes an invasive phenotype in melanoma. More importantly, the scratch test demonstrated the efficacy of the Nox inhibitor (DPI) in blocking migration, supporting its use to counteract drug resistance and thus cell invasion and metastasis in BRAF-mutated melanoma.
- |||||||||| Mekinist (trametinib) / Novartis
MEK-KINASE INHIBITOR (TRAMETINIB) AS A TREATMENT OPTION FOR HAIRY CELL LEUKEMIA () - May 12, 2023 - Abstract #EHA2023EHA_2872;
At the same time, the drug is effective in the absence of the MAP2K1 mutation (unlike vemurafenib, which effective only in the presence of the BRAFV600E mutation), and, like vemurafenib, trametinib monotherapy can be effective at a reduced dose (1 mg/day or 1 mg every other day). Kinase inhibitor, Treatment, MEK, Hairy cell leukemia
- |||||||||| Mekinist (trametinib) / Novartis
EFFICACY AND SAFETY OF TRAMETINIB IN ADULTS WITH LANGERHANS CELL HISTIOCYTOSIS AND ERDHEIM-CHESTER DISEASE (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_878;
In 5/8 (62,5%) patients AE resolved after dose reduction without efficacy impairment.? Diagnosis Gender Age Final trametinib dose Adverse events Previous therapy Follow up time, months Best response 1 ECD Male 33 Cycles 1 mg for 21 days than 7 days wash- out Skin rash, periorbital edema Interferon-alpha 2b 29 PR 2 ECD Female 38 1mg/day Skin rash Methylprednisolone, cyclophosphamide 28 PR 3 LCH and ECD Female 37 1 mg EOD Periorbital edema Prednisolone, cyclophosphamide, prospidine, vincristine, cytarabine, interferon, lenalidomide 31 PR 4 LCH Female 54 Cycles 1 mg for 25 days than 5 days wash- out Arthralgias, myalgias Vinblastine, prednisolone, vemurafenib, radiotherapy 19 CR 5 LCH Female 42 1 mg EOD Skin rash Sirolimus 18 N/A 6 ECD Male 46 1mg/day Skin rash, hypertension Nephrostomy only 12 N/A 7 LCH Male 40 1mg/day none Vinblastine, prednisolone, methotrexate, 6-MP, cladribine 11 CR 8 LCH Female 28 1mg/day Skin rash, fluid retention Treatment-na
- |||||||||| Real World Use of Systemic Therapy for Treatment of Advanced Thyroid Cancer (ENDOExpo) - May 11, 2023 - Abstract #ENDO2023ENDO_1664;
We identified patients with thyroid cancer who had prescription claims for at least one of the 15 SMKIs of interest (axitinib, cabozantinib, dabrafenib, entrectinib, everolimus, larotrectinib, lenvatinib, pazopanib, pralsetinib, selpercatinib, sorafenib, sunitinib, trametinib, vandetanib, and vemurafenib)...Since 2015 when lenvatinib was approved by the FDA for treatment of advanced differentiated thyroid cancer, it has become the most commonly prescribed SMKI for treatment of advanced thyroid cancer. However, variation exists in which SMKIs are used to treat patients with advanced thyroid cancer, with almost one-quarter of patients initiated on commercially available SMKIs.
- |||||||||| Enrollment change, Trial completion date, Trial termination, Trial primary completion date: Safety and Oversight of the Individually Tailored Treatment Approach: A Novel Pilot Study (clinicaltrials.gov) - May 10, 2023
P=N/A, N=3, Terminated,
Of the 74 approved drugs, 30 fail to comply with the rule of five. N=50 --> 3 | Trial completion date: Oct 2026 --> Dec 2022 | Recruiting --> Terminated | Trial primary completion date: Apr 2026 --> Dec 2022; low recruitment
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal, Heterogeneity, Metabolomic study: Quantifying Cell Heterogeneity and Subpopulations Using Single Cell Metabolomics. (Pubmed Central) - May 10, 2023
In addition, metabolites for each subpopulation can be prioritized. Combining the SCMS experimental technique with a bioinformatics tool, our label-free approach can be applied to quantitatively study cell heterogeneity, prioritize markers for further investigation, and improve the understanding of cell metabolism in human diseases and response to therapy.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Secretome Screening of BRAFV600E-Mutated Colon Cancer Cells Resistant to Vemurafenib. (Pubmed Central) - Apr 28, 2023
Accordingly, two proteins implicated in these processes including RPA1 and HSPA5/GRP78 were discussed in more details in the context of biological networks and their importance as potential secretome targets for further functional and clinical evaluation. Expression patterns of RPA1 and HSPA5/GRP78 in tumor tissues from colon cancer patients were also found in additional in silico analyses to be associated with BRAFV600E mutation status, which opens the possibility to extrapolate our findings and their clinical implication to other solid tumors harboring BRAFV600E mutation, such as melanoma.
- |||||||||| A randomized phase 2 trial of encorafenib + binimetinib + nivolumab vs ipilimumab + nivolumab in BRAFV600-mutant melanoma brain metastases: SWOG S2000. (On Demand | Hall A; Poster Bd # 360b) - Apr 26, 2023 - Abstract #ASCO2023ASCO_2577;
P2
In the Checkmate-204 trial of ipilimumab with nivolumab in MBM, the 6-month progression free survival (PFS) rate was 19% with a median PFS of only 1.2 months in symptomatic participants (those with neurological symptoms including steroids up to 4 mg/day of dexamethasone, n=18)...The single-arm phase 2 TRICOTEL study explored the triplet regimen of vemurafenib + cobimetinib + atezolizumab in MBM; in the symptomatic brain met cohort, 6-month PFS was 57% (n=24)...Funding: NIH/NCI grants U10CA180888, U10CA180819, U10CA180820 U10CA180868; and in part by Pfizer, Inc. Clinical trial information: NCT04511013.
- |||||||||| Tafinlar (dabrafenib) / Novartis, Tibsovo (ivosidenib) / Servier, Zelboraf (vemurafenib) / Roche
A powerful drug combination strategy targeting BRAF-mutant melanoma. (On Demand | Hall A; Poster Bd # 350) - Apr 26, 2023 - Abstract #ASCO2023ASCO_1852;
Background: BRAF inhibitors, such as vemurafenib and dabrafenib, are effective in treating patients with melanoma harboring (V600E) BRAF mutations...Further, the combination of AG-120 and dabrafenib was the most effective in vivo, reducing tumor growth in the BRAF-mutated melanoma xenograft model, and improving mouse survival compared to monotherapy controls. Our findings indicate that dual inhibition of mutated BRAF and wild-type IDH1 represents a novel treatment strategy for BRAF-mutated melanomas, with potential for application to other BRAF-mutated cancers (e.g., colon, hepatobiliary, thyroid, etc.).
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche, Tecentriq (atezolizumab) / Roche
Journal: Triple combinations of immunotherapy and targeted therapy in patients with melanoma with brain metastases. (Pubmed Central) - Apr 21, 2023
KEY MESSAGE: With the advent of these novel targeted therapies, it is prudent to be aware of cutaneous adverse events and the expected clinical course to alleviate the anxiety of our patients related to the diagnosis of keratinocytic cutaneous proliferation since the lesions are reversible No abstract available
- |||||||||| Zelboraf (vemurafenib) / Roche
Trial primary completion date, Combination therapy, Metastases: Phase II Trial of Vemurafenib and Sorafenib in Pancreatic Cancer (clinicaltrials.gov) - Apr 12, 2023
P2, N=12, Recruiting,
In particular, the BRAF inhibitors vemurafenib and dabrafenib, with or without rituximab, have revolutionized treatment of patients with relapsed or refractory disease. Trial primary completion date: Sep 2022 --> Sep 2023
- |||||||||| Zelboraf (vemurafenib) / Roche
Targeting tropomyosin receptor kinases induces DNA damage and apoptosis via NGFR-ROS signaling in cutaneous melanoma (Room 4 (60 seats, First Floor)) - Mar 28, 2023 - Abstract #EADO2023EADO_299;
K252a treatment induced a significantly higher melanoma cells mortality in two-dimensional cultures and in three-dimension melanoma spheroid models compared to the BRAF-inhibitor PLX-4032 (vemurafenib), regardless of BRAF-inhibitor sensitivity status (Figure 1b,d)... Trk inhibition and forced NGFR cleavage offer an interesting window of opportunity for advanced melanoma patients, warranting further studies.
- |||||||||| naporafenib (ERAS-254) / Erasca, tovorafenib (DAY101) / Day One Biopharma
Journal: Structure and RAF-family kinase isoform selectivity of Type II RAF inhibitors tovorafenib and naporafenib. (Pubmed Central) - Mar 26, 2023
Our findings have important clinical ramifications. Type II RAF inhibitors are generally regarded as Pan-RAF inhibitors, but our studies of these two agents, together with recent work with type II inhibitors belvarafenib and naporafenib, indicate that relative sparing of ARAF may be a property of multiple drugs of this class.
- |||||||||| Zelboraf (vemurafenib) / Roche
PK/PD data, Journal: New flavone-based arylamides as potential V600E-BRAF inhibitors: Molecular docking, DFT, and pharmacokinetic properties. (Pubmed Central) - Mar 25, 2023
Type II RAF inhibitors are generally regarded as Pan-RAF inhibitors, but our studies of these two agents, together with recent work with type II inhibitors belvarafenib and naporafenib, indicate that relative sparing of ARAF may be a property of multiple drugs of this class. The docking result demonstrated that four compounds (10, 11, 28, and 31) had acceptable docking scores (MolDock score of
- |||||||||| Trial completion date, Trial primary completion date, Tumor mutational burden: My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors (clinicaltrials.gov) - Mar 20, 2023
P2a, N=670, Active, not recruiting,
Additional studies could confirm these results for dasatinib, everolimus, pazopanib and ruxolitinib, and particularly for the two medicinal products with results slightly above the significance threshold, namely, crizotinib and vemurafenib, in our sensitivity analyses. Trial completion date: Sep 2023 --> May 2023 | Trial primary completion date: Sep 2023 --> May 2023
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