Tafinlar (dabrafenib) / Novartis, BeiGene - LARVOL DELTA

Nivolumab Induced Diabetic Ketoacidosis (ATS 2025) - "Oncology continued the patient on nivolumab as systemic adjuvant therapy was necessary, and an alternate regimen (dabrafenib plus trametinib) was not an option given the BRAF WT mutation of melanoma. Management of nivolumab-induced DKA generally follows conventional DKA treatment protocols. However, multidisciplinary collaboration involving oncologists and endocrinologists is crucial in determining the continuation or discontinuation of ICI therapy, as the patients may still benefit from continued treatment due to better cancer outcomes."

IO biomarker • Diabetes • Endocrine Disorders • Fatigue • Immunology • Infectious Disease • Melanoma • Metabolic Disorders • Mood Disorders • Nephrology • Oncology • Pneumonia • Renal Disease • Solid Tumor • Type 1 Diabetes Mellitus • BRAF

Resistance to Anti EGFR Through the Successive and Cumulative Acquisition of Two New Oncogenic Addictions: BRAF and ALK (ATS 2025) - "She received Gefitinib on the first line...Following progression on chemotherapy, the patient receives targeted therapies combining Dabrafenib, Trametinib and Osimertinib. Due to a dissociated response after 4 months of treatment, a 5th line of Paclitaxel Bevacizumab was initiated. Following a new progression and the presence of an ALK rearrangement on the re-biopsy, treatment with Alectinib was then proposed. The response was dissociated and a final line was therefore proposed before stopping active treatments for toxicity and deterioration in general condition. This case reports a resistance to anti-EGFR by the successive and cumulative acquisition of two new oncogene addictions and emphasizes the importance of rebiopsy at each progression on targeted therapy if feasible."

CNS Disorders • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Psychiatry • Solid Tumor • ALK • BRAF

Cardiomyopathy With BRAF/MEK Inhibitor Use in Non Small Cell Lung Cancer: A Rare Treatment-Related Adverse Event (ATS 2025) - "For patients with BRAF V600E-mutant NSCLC, the combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) has become a standard of care, demonstrating significant clinical benefit. The role of global longitudinal strain (GLS) as an early indicator of cardiac dysfunction could be significant, as it detects meaningful changes before a reduction in EF. Further research is needed to validate the utility of GLS in predicting and managing cardiotoxicity in patients receiving BRAF/MEK inhibitors to better predict impending cardiotoxicity."

Adverse events • IO biomarker • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • PD-L1

Extended Survival in Stage IV Papillary Thyroid Carcinoma presenting with Anaplastic Transformation (ENDO 2025) - "She briefly received chemotherapy with paclitaxel and carboplatin in November 2018 with RAI and anti-BRAF regimen of dabrafenib and trametinib from January to April 2019 which was discontinued for intolerance...The patient continues with follow-up almost 6 years from diagnosis on thyroid hormone suppression with levothyroxine. This case demonstrates an atypical course of anaplastic thyroid cancer... This case demonstrates an atypical course of anaplastic thyroid cancer. The patient had good response to surgery and chemoradiation and continues to fare well on thyroid hormone suppression almost 6 years from diagnosis, a very rare prognosis.Of note, the sigmoid colon uptake positive on initial PET CT disappeared on repeat imaging studies. It is unclear if the sigmoid colon uptake had been a false positive result or had resolved with treatment."

Metastases • Endocrine Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

IMM1104-101: A Phase 1/2a Study of IMM-1-104 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=320 | Recruiting | Sponsor: Immuneering Corporation | N=210 ➔ 320

Enrollment change • Colorectal Cancer • Hepatology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • APC • HRAS • KRAS

Outcomes of patients treated with dabrafenib and trametinib who developed pyrexia syndrome and severe/complicated pyrexia syndrome. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Palliative care

Is one year enough? Extended adjuvant dabrafenib plus trametinib for Chinese patients with resected stage III melanoma. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Melanoma • Oncology • Solid Tumor

Dabrafenib and trametinib vs anti-PD(L)1 for the adjuvant treatment of locally advanced BRAF-mutant melanoma: A systematic review and meta-analysis. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Metastases • Retrospective data • Review • Melanoma • Oncology • Solid Tumor • BRAF

Prognosis and survival evaluation in treating high-risk BRAF V600 mutation stage III or IV melanoma with dabrafenib plus trametinib therapy: A meta-analysis of 2,660 patients. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Retrospective data • Melanoma • Oncology • Solid Tumor • BRAF

Comparing the impact of nivolumab & ipilimumab combination therapy vs. dabrafenib & trametinib on outcomes in malignant melanoma patients: A global propensity-matched retrospective cohort study. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Combination therapy • Retrospective data • Melanoma • Oncology • Solid Tumor

The preliminary safety results of an observational phase II study of concurrent use of aspirin with dabrafenib and trametinib in BRAF V600 NSCLC. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT05988697 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Pilot study evaluating the addition of cemiplimab in BRAF-mutant anaplastic thyroid cancer after progression on dabrafenib and trametinib. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT04238624 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF

Early Access Program in oncology: Retrospective study at a Portuguese hospital (ECOP 2024) - "During the study period were submitted 163 EAP requests for abiraterone, amivantamab, bevacizumab, durvalumab, encorafenib, enfortumab, everolimus, erdafitinib, lenvatinib, lurbinectedin, niraparib, nivolumab, olaparib, pembrolizumab, pertuzumab, ramucirumab, sacituzumab govitecan, selpercatinib, trifluridine/tipiracil, trametinib+dabrafenib, trastuzumab-deruxtecan and tucatinib. Conclusion Most cases correspond to metastatic disease, EAPs facilitate timely access to innovative therapies for patients with high unmet medical needs. The majority of situations were financed, which confirms the importance of EAPs in an era where oncology is constantly innovating."

Retrospective data • Gastrointestinal Disorder • Oncology

Neoadjuvant pembrolizumab in combination with dabrafenib and trametinib (DTP) for BRAF V600E-mutated anaplastic thyroid cancer (BRAFm-ATC): A multicenter phase 2 trial. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT04675710 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Combination therapy • P2 data • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF

Dabrafenib and trametinib in the treatment of BRAF-mutated anaplastic thyroid cancers (ATC). (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF

Adverse effects of systemic advanced melanoma therapies-do BRAF/MEK inhibitors increase the incidence of mesenteric panniculitis? (PubMed, Eur Radiol) - "Question BRAF/MEK and immune checkpoint inhibitors have revolutionized melanoma treatment but are associated with various side effects, yet data regarding the development of mesenteric panniculitis are scarce. Findings BRAF/MEK inhibitor treatment is associated with a significantly higher rate of mesenteric panniculitis compared to immune checkpoint inhibitor treatment in advanced melanoma. Clinical relevance BRAF/MEK inhibitor-treated patients are at risk for development of mesenteric panniculitis. As this benign finding can mimic or conceal malignancy, awareness of it is important especially in these patients."

Adverse events • Journal • Melanoma • Oncology • Solid Tumor • CTLA4

COMBI-i: A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma (clinicaltrials.gov) - P3 | N=568 | Terminated | Sponsor: Novartis Pharmaceuticals | Completed ➔ Terminated; Sponsor decision

IO biomarker • Trial termination • Melanoma • Oncology • Solid Tumor • PD-L1

The efficacy of NST-628, a non-degrading pan-RAF/MEK molecular glue, and MEK inhibitors for overcoming acquired osimertinib resistance mediated by TRIM24-BRAF fusions in EGFR mutant NSCLC (AACR 2025) - "Next, we utilized a panel of compounds targeting the RAS/RAF/MAPK pathway including agents targeting pan-RAS (RMC-6236 and RMC-7977), SHP2 (RMC-4550), BRAF (dabrafenib, encorafenib, tovorafenib and vemurafenib), pan-RAF (TAK-632), MEK (binimetinib, cobimetinib, selumetinib and trametinib), pan-RAF/MEK (NST-628) and assessed whether targeting signal transduction molecule downstream of EGFR could overcome this adaptative resistance mechanism. TRIM24-BRAF expressing cells showed minimal sensitivity to BRAF, SHP2 or RAS targeting single agents. Taken together, our findings indicate that expression of TRIM24-BRAF fusion induce osimertinib resistance in EGFR mutant NSCLC and targeting the MEK pathway using trametinib or NST-628 can overcome osimertinib resistance in this setting."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • EGFR • TRIM24

Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma. (PubMed, Ann Oncol) - "Stage IIIA melanoma has a modest risk of recurrence. Adjuvant anti-PD1 did not significantly improve RFS or DMFS compared to OBS alone. Adjuvant TT appears promising over anti-PD1 or OBS. Outcomes after adjuvant therapy in this population needs further study in larger datasets with longer follow up or prospective randomised trials."

Journal • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

Integrating ctDNA and FDG-PET dynamics to predict pathological response following neoadjuvant systemic therapy in stage III melanoma (AACR 2025) - "For validation, FDG-PET SUVmax changes and ctDNA dynamics will be assessed in two trial cohorts: NeoTrio (N=45, pembrolizumab ± dabrafenib and trametinib) and NeoPele (N=20, pembrolizumab and Lenvatinib). Combining ctDNA dynamics with FDG-PET SUVmax changes can improve the prediction of pathological response to neoadjuvant therapy in stage III melanoma. This integrated approach could help identify patients who will achieve durable responses and can safely avoid surgery, supporting the development of more personalized treatment strategies."

Circulating tumor DNA • Clinical • FDG PET • IO biomarker • Melanoma • Oncology • Solid Tumor

Novel anaplastic thyroid carcinoma patient-derived xenograft models and cell line (AACR 2025) - "MDA-ATC8 is a BRAF wild type (WT) and TP53, NRAS_Q61K, TERT, ASXL2_G853S, ERBB4_D243N, INHBA_I410T mutant ATC model, from a patient previously treated with dabrafenib, trametinib and pembrolizumab (DTP). We report the development and establishment of three new ATC PDX models with one paired cell line. These models show excellent compatibility with their human tissue counterparts, making them highly reliable as preclinical models. Furthermore, with novel drugs being developed for RAS_Q61 mutation, MDA-ATC8 may play a major role in testing potential candidates for this untreatable patient population in the near future."

Preclinical • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • ABL1 • BRAF • FGFR2 • KMT2C • LRP1B • MEN1 • RAS • RICTOR • TP53

Global analysis of actionable genomic alterations in thyroid cancer and precision-based pharmacogenomic strategies. (PubMed, Front Pharmacol) - "Furthermore, our findings highlight the clinical potential of targeted drug inhibitors, including vandetanib, dabrafenib, and selumetinib, for improving treatment outcomes. Future efforts should focus on including underrepresented populations, developing population-specific prevention strategies, and fostering global collaboration to ensure equitable access to pharmacogenomic testing and innovative therapies. These initiatives have the potential to transform thyroid cancer care and align with the broader goals of personalized medicine."

Biomarker • Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF • EPHA7 • KRAS • NRAS

Molecular Testing and Targeted Therapies in Hepatobiliary Cancers: A Review. (PubMed, JAMA Surg) - "Moreover, multiple solid cancer tumor-agnostic therapies are approved (larotrectinib, entrectinib, and repotrectinib for NTRK fusions; selpercatinib for RET fusions; dabrafenib and trametinib combination for BRAF V600E mutations; dostarlimab or pembrolizumab for tumors with high microsatellite instability and pembrolizumab for tumor mutation burden ≥10 mutations/megabase), highlighting the need for NGS as well as ERBB2 (formerly HER2) immunohistochemistry (IHC) (with the recent approval of solid tissue-agnostic deruxtecan trastuzumab for ERBB2-positive [IHC 3+] cancer) across cancers. Tumor-agnostic and N-of-1 clinical trials have challenged traditional clinical trial paradigms and provide the foundation for truly personalized oncology for patients with these aggressive cancers. Further work is needed to determine how to leverage these novel approaches into the management of operable disease."

IO biomarker • Journal • Tumor mutational burden • Biliary Cancer • Biliary Tract Cancer • Hepatocellular Cancer • Hepatology • Microsatellite Instability • Oncology • Solid Tumor • BRAF • HER-2 • MSI • NTRK • RET • TMB

Modeling the Path to Cure: How (NEO)Adjuvant Drug Therapies are Evaluated in Health Technology Assessment (HTA) (ISPOR 2025) - "This review focused on non-small cell lung cancer (atezolizumab), melanoma (dabrafenib+trametinib), and early breast cancer (olaparib, pembrolizumab). A variety of cure modeling approaches have been employed with mixed receptivity. Thoughtful, integrated approaches across agencies would be beneficial to address key challenges such as variability in timepoint and cure assumptions within subgroups."

Clinical • Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Durable responses upon short-term addition of targeted therapy to anti-PD1 in advanced melanoma patients: 5-year progression-free and overall survival update of the IMPemBra trial. (PubMed, Eur J Cancer) - "This survival update from the IMPemBra trial demonstrates that combination of short-term TT and checkpoint inhibition can induce long-lasting responses, warranting further analyses in larger cohorts, and in a randomized design."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor