Koselugo (selumetinib) / Merck (MSD), AstraZeneca, Pfizer - LARVOL DELTA

Real-world clinical impact of selumetinib in adult patients with neurofibromatosis type 1 and plexiform neurofibromas: Preliminary results of the SCAN study (SNO 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Genetic Disorders • Neurofibromatosis • Solid Tumor

ADAM17-Driven NKG2D Ligand Shedding Defines a Leukemia-Intrinsic Immune Evasion Program That Predicts Venetoclax Resistance and Reveals MEK and PI3K as Therapeutic Vulnerabilities in AML (SOHO 2026) - "Drug vulnerability mapping identified MEK inhibitors (trametinib, selumetinib), the HDAC inhibitor panobinostat, and PI3K/AKT/mTOR inhibitors (GDC-0941, MK-2206, and INK-128) as selectively active in NK-high AML (all FDR <0.001). An ADAM17-centered NK immune evasion score identifies venetoclax-resistant AML across two independent cohorts and associates with a survival disadvantage equivalent to an 88% increase in hazard per SD of score. This phenotype is consistent with BCL2 independence and engagement of compensatory MAPK and PI3K survival signaling, nominating MEK and PI3K inhibitors as biologically therapeutic alternatives for refractory patients. Prospective biomarker-stratified trials are required before clinical implementation of this scoring approach."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • ADAM17 • BCL2 • HLA-E • NKG2D • SMAD3 • TGFB1 • TIMP3 • ULBP1 • ULBP2

Neurofibromatosis Type 1 (NF1) Associated Glioma Treated with Selumetinib: A Case Report (SNO 2026) - No abstract available

Case report • Clinical • Brain Cancer • Genetic Disorders • Glioma • Neurofibromatosis • Solid Tumor • NF1

Metabolism pathway-based subtyping in pancreatic adenocarcinoma: an integrated study by bulk RNA-sequence and machine learning algorithms. (PubMed, Int J Surg) - "Drug sensitivity analysis showed that the high-risk group was more sensitive to AZD6244, ABT737, and other drugs. This study stratified patients with PAAD into three subgroups based on metabolic pathways and prognostic information, revealing significant differences in clinical outcomes, immune characteristics, and genetic mutations. The robust RS model developed from these findings demonstrated strong predictive power for patient survival and identified promising therapeutic strategies, providing valuable insights for advancing precision medicine in PAAD."

Journal • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

SOLAR: Phase Ib Dose Expansion of Selumetinib (MEK Inhibitor) and OLAparib (PARP Inhibitor) Combination in Solid Tumors with RAS Pathway Alterations and in PARP Inhibitor-Resistant Ovarian Cancer (SGO 2023) - No abstract available

Late-breaking abstract • P1 data • Oncology • Ovarian Cancer • Solid Tumor

Randomised, Phase II study of selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer. (PubMed, Br J Cancer) - "Adding sequential or continuous selumetinib to CisGem failed to improve efficacy and increased toxicity in patients with advanced BTC."

Combination therapy • Journal • P2 data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Real-world mental health medication utilization pre- and post-selumetinib initiation among adult patients in the US: a retrospective claims database study (SNO 2026) - No abstract available

Claims database • Real-world • Real-world evidence • Retrospective data • Oncology

Surgical management of plexiform neurofibromas: An imaging-based perioperative framework. (PubMed, JPRAS Open) - "MEK inhibitors, including selumetinib, provide effective non-surgical therapy for progressive or unresectable PNs...An imaging-driven approach, selective use of embolization, and incorporation of intraoperative adjuncts can optimize tumor control and functional outcomes. Prospective multicenter studies are needed to standardize imaging protocols, surgical selection criteria, and long-term outcome reporting."

Journal • Review • Brain Cancer • Genetic Disorders • Hematological Disorders • Neurofibromatosis • Neurofibrosarcoma • Oncology • Pain • Solid Tumor • NF1

SARC031: A PHASE 2 TRIAL OF SELUMETINIB AND SIROLIMUS FOR PATIENTS WITH UNRESECTABLE OR METASTATIC MALIGNANT PERIPHERAL NERVE SHEATH TUMORS (CTOS 2022) - No abstract available

Clinical • P2 data • Brain Cancer • Neurofibrosarcoma • Oncology

Osimertinib plus Selumetinib in EGFR-Mutated Non-Small Cell Lung Cancer After Progression on EGFR-TKIs: A Phase Ib, Open-Label, Multicenter Trial (TATTON Part B). (PubMed, Clin Cancer Res) - "In this small study, AEs and tolerability of osimertinib plus selumetinib were as expected, on the basis of previous studies. The combination demonstrated antitumor activity supportive of further investigation in patients with MET-negative, EGFRm advanced NSCLC who had progressed on a previous EGFR-TKI."

Journal • Dental Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas (KOMET): a multicentre, international, randomised, placebo-controlled, parallel, double-blind, phase 3 study. (PubMed, Lancet) - P3 | "In the first international, randomised, placebo-controlled trial in adults with NF1-plexiform neurofibromas, selumetinib achieved a significant objective response rate versus placebo. No new safety concerns were identified. The observations of reduction in tumour volume by cycle 16, reduction in chronic and spike pain, reduction in analgesia, and decrease in pain interference over placebo show that selumetinib is effective at treating plexiform neurofibromas in adults with NF1."

Journal • P3 data • Brain Cancer • Genetic Disorders • Neurofibromatosis • Oncology • Pain • Solid Tumor • NF1

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer. (PubMed, Ann Oncol) - P1; "Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated."

IO biomarker • Journal • P1 data • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • Thoracic Cancer • EGFR

Case Report: Selumetinib as a neoadjuvant treatment for the removal of a PN. (PubMed, Front Pediatr) - "Selumetinib was discontinued 3 years post-surgery to evaluate tumor stability; however, tumor regrowth occurred, and the treatment was resumed. This case highlights the neoadjuvant role of selumetinib in transforming a tumor from inoperable to operable, resulting in a substantial improvement in the patient's quality of life."

Journal • Genetic Disorders • Neurofibromatosis • Oncology • Orthopedics • Pain • Solid Tumor • NF1

Using Patient iPSC-derived Retinal Pigment Epithelium to Evaluate Differential Susceptibility to MEK Inhibitor-Associated Retinopathy. (PubMed, Exp Eye Res) - "These exploratory findings support a testable hypothesis: that MEK inhibitor-Associated Retinopathy preferentially affects susceptible patients whose retinal pigment epithelium cannot sufficiently regulate expression of genes related to fluid transport and cell volume, altering the ability of these cells to properly function. Confirmation will require additional donor lines from each clinical phenotype."

Journal • Eye Cancer • Genetic Disorders • Neurofibromatosis • Oncology • Retinal Disorders • Solid Tumor • NF1

Latest Classification and Management of Circumscribed Astrocytic Gliomas (PubMed, No Shinkei Geka) - "Advances in precision oncology have transformed clinical management, and targeted therapies, such as dabrafenib/trametinib and everolimus, have been established; selumetinib received expanded adult approval in Japan in 2025. Moreover, next-generation type II RAF inhibitors, exemplified by tovorafenib, and emerging combinatorial approaches targeting pathway crosstalk offer promising strategies to overcome therapeutic resistance. This review synthesizes current molecular definitions and evolving personalized treatment paradigms for circumscribed gliomas. Integrating these molecular insights into routine practice is essential for optimizing tumor control and preserving neurological function in the CNS5 era."

Journal • Review • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Circumscribed Glioma • CNS Tumor • Glioma • Glioneuronal Tumor • Oncology • Solid Tumor • BRAF • PRKCA

NF113: Study of Cabozantinib With Selumetinib for Plexiform Neurofibromas (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Girish Dhall, MD | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Neurofibromatosis • Solid Tumor • NF1

A Phase 2 Study of Osimertinib in Combination With Selumetinib in EGFR Inhibitor nave Advanced EGFR Mutant Lung Cancer (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

TEAD inhibitors re-sensitize drug-resistant NF1 MPNST cells to MEK inhibitors. (PubMed, MicroPubl Biol) - "NF1 neurofibromas are treated with MEK inhibitors, such as mirdametinib and selumetinib, because they are driven by activation of the Ras/Raf/MEK/ERK signaling pathway. The cells were resistant to 15 other MEK inhibitors in a high-throughput screen but were re-sensitized by co-treatment with a TEAD inhibitor. These results suggest that TEAD inhibitors synergize with MEK inhibitors to overcome resistance and enhance therapeutic efficacy in MPNSTs."

Journal • Brain Cancer • Genetic Disorders • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • NF1

Risk of developing malignant peripheral nerve sheath tumors in patients with neurofibromatosis 1 receiving MEK inhibitor treatment for plexiform neurofibromas. (PubMed, Neurooncol Adv) - "Our data do not demonstrate a significant difference in the risk of MPNST development between patients with NF1-PN who received MEKi and non-MEKi treatments. Radiation exposure was significantly associated with a higher risk of MPNST development."

Journal • Brain Cancer • Genetic Disorders • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • NF1

Trial of Selumetinib and Bromodomain Inhibitor With Durvalumab for Sarcomas (clinicaltrials.gov) - P2 | N=41 | Recruiting | Sponsor: University of Alabama at Birmingham | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor

Efficacy of redifferentiation therapy in radioactive iodine refractory thyroid cancer: a systematic review and meta-analysis. (PubMed, Eur J Nucl Med Mol Imaging) - "In patients with RAI-refractory thyroid tumors, redifferentiation therapy using mitogen-activated protein kinase inhibitors successfully restores radioiodine avidity in approximately half of the cases. Although short-term disease control rates are promising, statistically significant prognostic differences and long-term survival benefits remain to be demonstrated in larger, standardized trials with extended follow-up."

Journal • Retrospective data • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Malignant peripheral nerve sheath tumor development during MEK inhibitor treatment: A pre-clinical study and a clinical case series. (PubMed, Neurooncol Adv) - P1/2 | "All were at increased risk for developing MPNST based on a large PN tumor burden, NF1 microdeletion, or presence of a pre-malignant atypical neurofibroma prior to starting selumetinib treatment. While these findings do not indicate acceleration of MPNST development on selumetinib, patients receiving MEKi for PN, in particular those with high-risk features, remain at risk for malignant transformation and should be monitored accordingly."

Journal • Preclinical • Brain Cancer • Genetic Disorders • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • NF1

Long-Term Hematologic Effects of Selumetinib Treatment in Children With Neurofibromatosis Type 1-Associated Plexiform Neurofibromas. (PubMed, Pediatr Blood Cancer) - P1/2 | "There was a statistically significant, but unlikely clinically significant, decrease in absolute lymphocyte count and an increase in mean corpuscular volume. Selumetinib was not associated with apparent clinically significant hematologic changes."

Journal • Genetic Disorders • Hematological Disorders • Neurofibromatosis • Pediatrics • Solid Tumor

Drug-induced paronychia: a disproportionality and time-to-onset pharmacovigilance study using FAERS and JADER. (PubMed, Cutan Ocul Toxicol) - "The ten drugs with the strongest disproportionality signals (ranked by ROR) were Dacomitinib [ROR 374.77; 95% CI 276.31-508.31], Selumetinib [304.66; 228.55-406.10], Afatinib [296.98; 264.27-333.74], Panitumumab [204.37; 183.10-228.11], Amivantamab [167.61; 124.71-225.26], Necitumumab [151.38; 67.14-341.35], Mobocertinib [117.03; 71.21-192.34], Erdafitinib [59.36; 33.57-104.99], Lapatinib [48.09; 39.71-58.24], and Gefitinib [47.28; 37.09-60.27]...Time-to-onset analysis of 30 drugs with valid TTO data revealed that median onset times ranged from 4 days (Necitumumab) to 575.5 days (Alendronate), with several of the most frequently reported EGFR and MEK inhibitors exhibiting an early-failure pattern (Weibull β < 1), supporting concentrated monitoring during the first weeks of therapy...These findings, derived from spontaneous reporting data, indicate associations rather than causal risk and require further clinical and epidemiologic evaluation. The signals identified may..."

Adverse events • Journal • Oncology • Pain

A three-gene signature correlated with MAPK/ERK activation characterizes acquired resistance to EGFR-tyrosine kinase inhibitors in non-small cell lung cancer. (PubMed, Oncol Lett) - "Functional analyses further demonstrated that the pharmacological inhibition of MAPK/ERK signaling using selumetinib effectively re-sensitized AR cells to both afatinib and osimertinib, as demonstrated by restored drug sensitivity in CCK-8 assays. Collectively, these findings suggest that MAPK/ERK signaling contributes to the transition from adaptive tolerance to stable resistance to afatinib and highlight a tractable therapeutic vulnerability for overcoming resistance to tyrosine kinase inhibitors in NSCLC."

Gene Signature • Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HSPA1A