Tafinlar (dabrafenib) / Novartis, BeOne Medicines - LARVOL DELTA

The molecular landscape of patients with malignant histiocytosis (ASH 2025) - "Responders received a range of agents matched to their mutations: trametinib ( BRAFV600E, MAP2K1F53I, KRASQ16H/PTEND24G/EPHB1R327C, MAP2K1F53I/BCL2/CDKN1B/KIT, and CALR), dabrafenib + trametinib( BRAFG596R/KRASQ61H) , imatinib ( MAP2K1C121S/METG28881T/DUSP2G137D/HIST1H3BC97Y/GRIN2AS1216C and PTPN11/STK11/GNA11/JAK2) , chidamide + sintilimab( IDH2G515A/RHOAG50T/TET23344delC), sirolimus( PTEN/FGFR3/SETD2) and sorafenib ( BRAFD594G/KRASK117N/TP53). Despite this complexity, durable clinical responses to targeted agents are achievable, even in heavily mutated cases. These findings support the use of comprehensive genomic profiling in MH to identify therapeutic targets and guide precision treatment strategies."

Clinical • IO biomarker • Sarcoma • Solid Tumor • ADGRG6 • BCL2 • BCL6 • BRAF • CALR • CDK1 • CDKN1A • CDKN1B • CDKN2A • CDKN2B • CREBBP • CYTOR • DNMT3A • EGFR • FGFR3 • GNA11 • JAK2 • KRAS • MAP2K1 • NF1 • NRAS • NRF1 • PTEN • PTPN11 • SETD2 • STK11 • TET2 • TP53

9-year-old female presenting with l lower leg pain diagnosed with erdheim-chester disease (ECD) (ASH 2025) - "Cytokine panel was remarkable for elevation in IL6, and patient received bridging therapy with tocilizumab infusion. As no standard treatment guideline exist for pediatric patients with ECD, case reports have focused on use of and outcomes of therapies such as steroids, chemotherapy, interferon alfa and targeted biologics in attempt to better optimize treatment (Pegoraro et al., 2023). The aim of this report is to further highlight how ECD can present in pediatric populations and present treatment response to dabrafenib and targeted cytokine inhibition in a pediatric patient with BRAFV600E mutation and diffuse bony involvement."

Pain • Rare Diseases • IL6

Consolidation of dual MAPK inhibitor therapy by allograft in histiocytic sarcoma: A report of two cases (ASH 2025) - "Transplant proceeded using fludarabine 150mg/m 2 and melphalan 140mg/m 2 with post-grafting cyclophosphamide, mycophenolate mofetil and tacrolimus for graft-versus-host disease (GvHD) prophylaxis...He remains well on dabrafenib and trametinib in CMR at 16-months post-transplant...To consolidate this response, allograft from a haploidentical donor was performed using fludarabine 150mg/m 2 and melphalan 140mg/m 2 with post-grafting cyclophosphamide and ciclosporin for GvHD prophylaxis... These 2 cases suggest that allograft is feasible on dual MAPK inhibitor therapy and may have potential efficacy as consolidation for high-risk visceral HS. Withdrawal of inhibitors and longer follow up are required to determine the durability of remission with this approach."

Clinical • Cough • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Infectious Disease • Respiratory Diseases • Sarcoma • Solid Tumor • Tuberculosis • BCL6 • CCND1 • CD14 • CD163 • CD1a • KRAS • MAP2K1

Remission instead of eradication? MEK inhibition in primary refractory childhood LCH (ASH 2025) - "Patient and Methods We report on a 9-month-old infant with multisystemic LCH (thymus and cervical lymph nodes) who progressed under vinblastin/prednisone and did not respond to second-line cytarabine/vincristine therapy...This class confers resistance to first-and second generation BRAF inhibitors (e.g., Vemurafenib, Dabrafenib), which preferentially target monomeric BRAFV600E but not dimer-dependent BRAF. Functional ex vivo drug sensitivity profiling demonstarted superior tumor cell cytotoxicity of cobimetinib compared to other tested agents, including BRAF inhibitors and alternative MEK1/2 inhibitors, such as trametinib and selumetinib...However, the risk of clonal persistence underscores the need for integrated strategies. Future studies should investigate rational combinations of MEK inhibitors with senolytics and/or mTOR blockade to target both MAPK signaling and senescent cell survival, thereby suppressing SASP-related inflammation, aiming for durable molecular..."

Clinical • Hematological Malignancies • Langerhans Cell Histiocytosis • ARAF

KRAS mutations in histiocytic neoplasms: Mutation spectrum and response to MEK inhibition (ASH 2025) - "Regarding treatment, 57% (13/23) received MEKi, all initially cobimetinib, with 1 patient switched to trametinib due to progression. Of the 10 patients who did not receive MEKi, 1 was treated with vemurafenib for a concurrent BRAF p.V600E mutation; 3 remained on observation; 2 underwent surgery without recurrence; 3 received other systemic therapies including corticosteroid, methotrexate, rituximab, lenalidomide, or sirolimus; and 1 developed diffuse large B-cell lymphoma, treated with R-CHOP...A retrospective cohort described an ECD patient with p.K117N achieving PR on dabrafenib and trametinib with a concurrent BRAF mutation and another with p.G12A achieving PR on trametinib...As MEKi acts downstream, efficacy likely depends on the level of pathway activation conferred by specific KRAS variants. Larger studies are needed to confirm these observations and identify mutation-specific predictors to guide personalized treatment."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Langerhans Cell Histiocytosis • Lymphoma • Non-Hodgkin’s Lymphoma • Rare Diseases • ARAF • KRAS • MAP2K1 • NRAS • PIK3CA

Phase 2 trial of encorafenib plus binimetinib for patients with BRAF V600 mutated relapsed/refractory hairy cell leukemia (ASH 2025) - "Background : Hairy cell leukemia (HCL) is an indolent B-cell leukemia characterized by durable completeremissions to purine analogs cladribine or pentostatin, but repeated relapses and cumulative toxicity torepeated purine analog courses...Vemurafenib was combined with rituximab,achieving 57% MRD-free CRs... Encorafenib-binimetinib is highly effective in relapsed/refractory HCL and was well toleratedwhen dose reductions occurred as needed. Compared to dabrafenib-trametinib, the lower incidence offever (11% vs 58%, p<0.0001) is a major advantage. The CR rate of 93% without rituximab isunprecedented for BRAF inhibition in HCL."

Clinical • P2 data • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Melanoma • Musculoskeletal Pain • Pancreatitis • Retinal Disorders • Solid Tumor • BRAF

Discontinuation of targeted therapy in histiocytic neoplasms with durable response: A multicenter retrospective study (ASH 2025) - "Targeted therapies include BRAFi (n=5, 19.2%; 2 dabrafenib, 3 vemurafenib), MEKi(n=17, 65.4%; 14 cobimetinib, 3 trametinib), and BRAF/MEKi (n=4, 15.4%; 3 dabrafenib/trametinib, 1vemurafenib/cobimetinib). In patients with histiocytic neoplasm and prior durable response to targeted therapy, ~40%experienced disease progression after treatment discontinuation. BRAF V600E mutation and CNS diseaseare associated with inferior PFS, suggesting these subgroups may not be appropriate for limited durationof treatment. Novel approaches are needed in these high-risk patients."

Retrospective data • CNS Disorders • Langerhans Cell Histiocytosis • Rare Diseases • ASXL1 • MAP2K1 • NRAS • SRSF2

Safety profile of dabrafenib plus trametinib (D+T) in previously treated Chinese Mainland subgroup (CMS) population with radioactive iodine (RAI)–refractory BRAF V600E mutation–positive differentiated thyroid cancer (DTC) (ESMO Asia 2025) - P3 | "D+T therapy was tolerable in CMS pts with RAI-refractory BRAF V600E mutation-positive DTC, who received prior VEGFR targeted-therapy, with safety profile consistent with global studies of other indications."

Clinical • Brain Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF

Retrospective study of dabrafenib and trametinib in advanced BRAF V600E-mutant thyroid cancer: Efficacy in neoadjuvant and RAIR settings (ESMO Asia 2025) - "DabTram exhibits significant activity in downsizing tumors and enabling organ-sparing surgery in advanced PTC. First-line use in RAIR patients shows promising tumor responses, warranting further investigation for long-term survival benefits. Larger prospective studies are needed to validate these findings."

Metastases • Retrospective data • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF

Redifferentiation of radioiodine-refractory metastatic differentiated thyroid carcinoma with BRAFV600E mutation by dabrafenib in combination with trametinib (ESMO Asia 2025) - P=N/A | "Dabrafenib combined with trametinib can induce redifferentiation by stimulating radioiodine uptake in patients with BRAF V600E -mutant radioactive iodine-refractory metastatic papillary thyroid carcinoma, suggesting an optional therapeutic strategy for this patient population."

Combination therapy • Metastases • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF • TG

MULTISARC: Molecular Profiling of Advanced Soft-tissue Sarcomas (clinicaltrials.gov) - P3 | N=603 | Active, not recruiting | Sponsor: Institut National de la Santé Et de la Recherche Médicale, France | Trial completion date: Oct 2025 ➔ Jan 2026

IO biomarker • Trial completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Phase 2 study of combined therapy FOLFOX with dabrafenib and cetuximab/panitumumab as first-line treatment for patients with metastatic colorectal cancer MSS with BRAF V600E mutation. (ASCO-GI 2026) - P2 | "Clinical Trial Registration Number: NCT06978400 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF

Advances in Tissue-Agnostic Targeting in Cancer Therapeutics: Current Approvals, Challenges, and Future Directions. (PubMed, Oncol Res) - "The purpose of this review is to explore the impact, safety, and challenges of tissue-agnostic therapies including pembrolizumab, dostarlimab, larotrectinib, entrectinib, repotrectinib, dabrafenib plus trametinib, selpercatinib, and trastuzumab deruxtecan. We discuss emergence of pan-histological biomarkers, such as neoantigen burden, current updates on trials as well as trial outlining strategies to refining patient selection, while also supporting broader access to biomarker testing. Collectively, these insights underscore the transformative role of tissue-agnostic therapies in precision oncology while emphasizing the ongoing need for research to optimize their application and overcome current barriers."

Biomarker • Journal • Pan tumor • Review • Oncology

An atlas of ex vivo drug sensitivity profiles in 666 clinical glioblastoma samples revealed distinct survival-associated networks (SNO 2025) - P=N/A | "Eleven drugs were tested, including DNA-damaging agents (lomustine, carboplatin, temozolomide, procarbazine, irinotecan, etoposide) and targeted agents (abemaciclib, dabrafenib, osimertinib, rucaparib, trametinib). Longitudinal sampling revealed dynamic changes in drug sensitivity, reflecting evolutionary tumor biology. This ex vivo drug sensitivity atlas reveals distinct, non-random survival-associated clustering patterns that reflect underlying glioblastoma cellular physiologies and may inform future clinical trial designs."

Preclinical • Brain Cancer • Glioblastoma • Glioma • Solid Tumor

Emerging Targeted Therapies and Ongoing Clinical Trials in Pediatric Brain Tumors (PubMed, No Shinkei Geka) - "Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus..."

Journal • Review • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • High Grade Glioma • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • BRAF • KIAA1549 • NF1 • NTRK

Precision Medicine in Pediatric Neuro-Oncology-Experience from a tertiary care center in Canada. (SNO 2025) - "Monotherapy with MEK inhibitors (Trametinib, Selumetinib, N=30/50, 60%) was the most common regime; 12 different combinations of TT were used; most common being Dabrafenib and Trametinib. Our study confirms existing data in the literature regarding precision medicine in pediatric cancer with high CBR along with good quality of life and minimal toxicities."

Clinical • Brain Cancer • Glioma • Pediatrics • Solid Tumor

Efficacy of Small Molecule Kinase Inhibitors in Histiocytic Neoplasms with Non-BRAFV600E Mutations: Concordance of Pre-Clinical Predictions to Clinical Responses (ASH 2024) - "Preclinical studies suggest class I, but not classes II-III, BRAF mutations are sensitive to RAF monomer inhibitors (dabrafenib, encorafenib, vemurafenib) while classes I-II, but not class III, BRAF mutations are sensitive to MEK inhibitors (Yaeger R, Cancer Discovery 2019). In contrast, RAF-regulated MAP2K1 mutants have variable sensitivities to allosteric MEK inhibitors (binimetinib, cobimetinib, selumetinib, trametinib) while RAF-dependent and RAF-independent MAP2K1 mutations are resistant...Among those with BRAF class II mutations, 2 received vemurafenib and had NR, while 9 received MEK inhibitors (binimetinib, cobimetinib, trametinib) and most responded (3 CRs, 5 PRs)...There was concordance of efficacy in the setting of BRAF classes I-III and MAP2K1 RAF-regulated mutations. However, we found discordant findings in patients harboring RAF-dependent and RAF-independent MAP2K1 mutations as well as KRAS mutations as most responded to allosteric MEK inhibitors."

Discordant • Preclinical • Langerhans Cell Histiocytosis • Rare Diseases • BRAF • KRAS • MAP2K1 • NRAS

BRAF V600E in Thyroid Cancer: Navigating Prognostic Uncertainty and Therapeutic Innovation. (PubMed, Eur Thyroid J) - "Selective BRAF and MEK inhibitors-including vemurafenib, dabrafenib, and selumetinib-have demonstrated efficacy in advanced thyroid cancers. The combination of dabrafenib and trametinib is FDA-approved for BRAF V600E-mutant anaplastic thyroid carcinoma (ATC) based on its significant survival benefits...Additionally, redifferentiation strategies using MAPK inhibitors to restore RAI avidity have shown promise, particularly in selected patients. These advances highlight the need to contextualize BRAF mutation status within a broader molecular and clinical framework to guide personalized, effective treatment strategies."

Journal • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF

Dabrafenib plus trametinib in an elderly patient with BRAF V600E-mutant advanced pancreatic adenocarcinoma: A case report. (PubMed, Front Oncol) - "At the time of drafting this report, the patient had achieved 8 months of PFS. This case suggests that dose-adjusted dabrafenib combined with trametinib might be a potentially effective treatment strategy for elderly patients with advanced pancreatic adenocarcinoma harboring BRAF V600E mutations."

Clinical • Journal • Melanoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • BRAF

Mesenteric Panniculitis Mimicking Metastases From Melanoma on FDG PET/CT in a Pediatric Patient Receiving Immunotherapy. (PubMed, Clin Nucl Med) - "A 16-year-old girl with metastatic melanoma, treated with nivolumab, dabrafenib, and trametinib, presented with abdominal pain and vomiting. Initial CT suggested metastases, showing mesenteric stranding and targetoid lesions. FDG PET/CT confirmed increased FDG uptake in the same region, but subsequent MRI and follow-up findings pointed to mesenteric panniculitis."

Journal • Melanoma • Oncology • Pain • Pediatrics • Solid Tumor

Efficacy of Targeted Agents and Immune Checkpoint Inhibitors in Patients with Malignant Histiocytosis (ASH 2024) - "TAs included BRAF inhibitor (vemurafenib [1]), MEK inhibitors (binimetinib [1], cobimetinib [2], trametinib [2]) and others (dasatinib [1], pazopanib [1], pexidartinib [1]), while ICIs were exclusively pembrolizumab (5)...TAs included BRAF inhibitor only (vemurafenib [3], dabrafenib [3]), MEK inhibitor only (trametinib [5]), BRAF + MEK inhibitors (2), and others (apatinib, anlotimib, bevacizumab, daratumumab, dasatinib, imatinib, pazopanib, sorafenib, or combinations [9]), while ICIs included pembrolizumab (4), nivolumab (4), tislelizumab (1), and sintilimab (1)...Conclusion TAs and ICIs can be considered in the management of MH. The responses to ICI therapy may be associated with the degree of PDL1 expression"

Checkpoint inhibition • Clinical • IO biomarker • Hematological Malignancies • Oncology • Sarcoma • Solid Tumor • DOCK8 • MAP2K1 • PD-L1 • PTPN11

BRAF V600E-MUTATED GASTROINTESTINAL STROMAL TUMORS: A CASE SERIES AND ANALYSIS OF IMMUNE TUMOR INFILTRATE (CTOS 2025) - "Patient A received vemurafenib for 21 months achieving an initial response, followed by gradual progression. He subsequently received dabrafenib/trametinib for 8 months with stable disease initially followed by slow progression. Ipilimumab/nivolumab was initiated and achieved a durable complete response, remaining disease-free for 6.5 years off therapy. Patient B received binimetinib/encorafenib for 26 months showing an initial mixed response with regression of the primary tumor but progression of hepatic metastases... BRAF mutant GISTs are rare with variable responses to BRAF/MEK inhibition. A durable complete response to ICI was observed in one patient. Preliminary immune profiling supports further investigation of immunotherapy in selected cases with immune-infiltrated microenvironments."

Clinical • IO biomarker • Stroma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Hepatocellular Cancer • Oncology • Sarcoma • BRAF • CD20 • CD8 • EP300 • FLT4 • JAK3 • LAG3 • NF1 • PD-1 • PD-L1 • RB1 • TSC2

Identification of MFSD3 as a potential prognostic biomarker of cervical cancer. (PubMed, Discov Oncol) - "Our study revealed that MFSD3 may serve as a potential prognostic biomarker for CC."

Biomarker • Journal • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor

Exploiting metabolic adaptations to overcome dabrafenib treatment resistance in melanoma cells. (PubMed, Mol Oncol) - "This PEITC effect could be demonstrated in two further dabrafenib-resistant cell lines, WM164D and 451LuP. These results suggest that the altered redox status is linked to compromised mitochondria and is associated with the development of BRAFi resistance, rendering cells exquisitely sensitive to the actions of selective ROS-inducing therapeutics."

Journal • Melanoma • Oncology • Solid Tumor • MAPK8

Response to dabrafenib and trametinib combined with pembrolizumab in an elderly patient with lung adenocarcinoma of unknown primary harboring BRAF V600E mutation and high PD-L1 expression: a case report. (PubMed, Front Immunol) - "The patient received combined dabrafenib, trametinib, and pembrolizumab with close safety monitoring, achieving rapid tumor control and complete remission by six months with manageable toxicity. This case suggests that early integration of PD-1 blockade with BRAF/MEK inhibition treatment may benefit selected patients and underscores the value of comprehensive molecular and immunohistochemical assessment to guide individualized therapy."

IO biomarker • Journal • Cardiovascular • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • PD-L1