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

A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma (clinicaltrials.gov) - P3 | N=300 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

Enrollment closed • Astrocytoma • Brain Cancer • Glioma • Oncology • Solid Tumor • BRAF • IDH1 • NF1

Selumetinib for Adults with NF1-Associated Plexiform Neurofibromas: Insights from the KOMET Study. (PubMed, Neuro Oncol) - No abstract available

Journal • Neurofibromatosis • Solid Tumor • NF1

A Pediatric Case of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumor of the Scalp. (PubMed, Plast Reconstr Surg Glob Open) - "The patient was treated preoperatively with selumetinib for size reduction, and the procedure was bloody...Immunohistochemistry revealed loss of H3K27me3 expression, indicative of aggressive tumor biology. The patient underwent adjuvant chemotherapy followed by a re-excision of the surgical site, which showed no residual tumor."

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

Integrative genomic and bioinformatic prioritization of drug repurposing candidates for prostate cancer. (PubMed, BMC Pharmacol Toxicol) - "Integrating genomics, bioinformatics, and molecular docking provides an effective strategy for identifying and prioritizing drug repurposing candidates in prostate cancer. Estradiol-benzoate, estradiol-cypionate, and selumetinib emerge as promising candidates, meriting further preclinical and clinical evaluation for advanced prostate cancer therapy."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • MAP2K1

Selumetinib in Adult Neurofibromatosis 1 with Plexiform Neurofibroma. (PubMed, Pharmaceuticals (Basel)) - "MEK inhibitors, including selumetinib and mirdametinib, have recently changed the treatment paradigm for these tumors. Selumetinib was well tolerated in our patient, with an asymptomatic Grade 3 CPK elevation that subsequently improved with a dose reduction. Our case adds to the growing body of evidence suggesting that selumetinib is effective and well tolerated in adult patients with NF1-associated PNs."

Journal • Genetic Disorders • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • NF1

Observational Study to Evaluate the Effect and Safety of Selumetinib in Pediatric Patients With NF1-PNs (clinicaltrials.gov) - P=N/A | N=409 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2027 ➔ May 2027 | Trial primary completion date: Nov 2027 ➔ May 2027

Enrollment closed • Trial completion date • Trial primary completion date • Genetic Disorders • Neurofibromatosis • Pediatrics • Solid Tumor

The Combination of HSP90 Inhibitors and Selumetinib Reinforces the Inhibitory Effects on Plexiform Neurofibromas. (PubMed, Cancers (Basel)) - " We demonstrated that combining selumetinib and SNX-2112 or retaspimycin can achieve better tumor inhibition with synergistic effects. The combination significantly delays the progression of mouse pNFs. The combination of selumetinib and HSP90i has significant synergistic effects, provides therapeutic inhibitor effects, and reduces the selumetinib dosage in combination."

Journal • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • Transplantation • CDC37 • NF1

AstraZeneca results: H1 and Q2 2025 (AstraZeneca) - "Total Revenue up 11% to $28,045m, driven by double-digit growth in Oncology and BioPharmaceuticals...The stable Gross Margin (Reported and Core) in H1 2025 was a result of: Positive effects from geographic mix; Negative effects from product mix. The rising contribution of Product Sales with profit sharing arrangements (Lynparza, Enhertu, Tezspire, Koselugo) has a negative impact on Gross Margin because AstraZeneca records Product Sales in certain markets and pays away a share of the gross profits to its collaboration partners."

Commercial • Asthma • Breast Cancer • Chronic Obstructive Pulmonary Disease • Dermatology • Endometrial Cancer • Gastric Cancer • Glioblastoma • Inflammation • Neurofibromatosis • Non Small Cell Lung Cancer • Prostate Cancer

MAZEPPA: Maintenance With Olaparib or Selumetinib + Durvaluma for m-PDAC Guided by BRCAness and KRAS Status. (clinicaltrials.gov) - P2 | N=307 | Active, not recruiting | Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • BRCA • KRAS

Selumetinib in pediatric patients with neurofibromatosis type 1 and plexiform neurofibroma: Propensity score analysis of SPRINT vs. natural history control arm. (PubMed, Neurooncol Adv) - P, P1/2 | "ClinicalTrials.gov, NCT01362803. Registered May 27, 2011, https://clinicaltrials.gov/study/NCT01362803."

Journal • Genetic Disorders • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • NF1

Identification of key ferroptosis-related genes associated with the development of gastric cancer: Prognostic models, molecular mechanisms and potential treatment strategies. (PubMed, Oncol Lett) - "Finally, using the Genomics of Drug Sensitivity in Cancer and Cancer Therapeutics Response Portal databases, potential drugs [(5Z)-7-oxozeaenol, selumetinib, RDEA119, AZ628, dabrafenib and trametinib] were identified based on the aforementioned seven key carcinogenic genes, focusing on those that targeted multiple genes. In conclusion, the present study identified 14 key ferroptosis-related genes, and seven key carcinogenic genes, which represent promising novel molecular targets for the prognosis and treatment of GC."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • AKR1C2 • GABARAP • GABARAPL2 • GJA1 • MIR484 • MIR675 • NOX4 • NOX5

Targeted therapy combinations with ipatasertib in multi-cell type 3D tumor spheroid models. (PubMed, Acad Oncol) - "The combination of ipatasertib with the MEK inhibitor selumetinib or the ERK inhibitor ravoxertinib resulted in additive and/or greater-than-additive cytotoxicity in approximately half the cell lines screened. The V600E mutation-specific BRAF inhibitor vemurafenib and the KRAS G12C selective inhibitor sotorasib in combination with ipatasertib were active in the eight BRAF V600E and four KRAS G12C mutant-containing cell lines, respectively. Vertical inhibition of the PI3K/AKT/mTOR pathway with the mTORC1/2 kinase inhibitor sapanisertib demonstrated additive and/or greater-than-additive effects in multiple cell lines. In early experiments, there was a correlation between the response to ipatasertib and selumetinib in two patient-derived tumor lines grown as mct-spheroids and the corresponding patient-derived xenografts. All data are accessible via the PubChem BioAssay public database."

Journal • Oncology • KRAS

Paronychia in Selumetinib-treated patients (EADV 2025) - No abstract available

Clinical • Dermatology • Pediatrics

Koselugo: Regulatory decision for adult neurofibromatosis-type 1 plexiform neurofibromas (based on KOMET trial) in H2 2025 (AstraZeneca) - H1 and Q2 2025 Results

Approval • Neurofibromatosis • Oncology

Neurofibromatosis Type 1 and MEK Inhibition: A Comprehensive Review with Focus on Selumetinib Therapy. (PubMed, J Clin Med) - "While the therapeutic potential of selumetinib has been demonstrated in preclinical and clinical studies, including those involving Japanese patients, this review aims to evaluate its application in real-world clinical practice. A comprehensive discussion of the case study provides insights into the efficacy, safety, and clinical challenges associated with selumetinib treatment, offering valuable perspectives for its use in managing NF1."

Journal • Review • Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor • NF1

Comment on: "selumetinib use as targeted therapy for plexiform neurofibroma: a comprehensive review of the literature" - mirdametinib as the emerging standard in NF1-PN. (PubMed, Orbit) - No abstract available

Journal • Neurofibromatosis • Solid Tumor • NF1

A Phase 2 Study of Osimertinib in Combination With Selumetinib in EGFR Inhibitor naïve Advanced EGFR Mutant Lung Cancer (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: Jun 2025 ➔ Dec 2025

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

A momentous progress update: epidermal growth factor receptor inhibitors as viable agents for combating cancer. (PubMed, RSC Med Chem) - "However, clinically used EGFRs such as apatinib, selumetinib, gefitinib, vandetanib, and erlotinib are not selective, thereby resulting in troublesome side effects. Preclinical, clinical, structure-activity relationships (SAR) with mechanism-based and in silico research, and other relevant data are compiled to offer directions for the scientific discovery of novel EGFR inhibitors with conceivable uses in therapy. The research trajectory of this entire field will provide incessant opportunities for the discovery of novel drug molecules with improved efficacy and selectivity."

Journal • Review • Breast Cancer • Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • ERBB4 • HER-2

Koselugo: Newly added patent in Orange Book (Orange Book) - Expiry on Mar 26, 2029

Patent • Genetic Disorders • Neurofibromatosis • Rare Diseases

Molecular mechanism and biological pathway of high-expressed RAD51 in regulating cell adhesion and potentially affecting oral squamous cell carcinoma. (PubMed, Discov Oncol) - "High expression of RAD51 may promote the advancement of OSCC by regulating the related mechanisms of cell adhesion."

Journal • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • CD74 • RAD51

A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma (clinicaltrials.gov) - P3 | N=220 | Recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Recruiting

Enrollment open • Head-to-Head • Astrocytoma • Brain Cancer • Genetic Disorders • Glioma • Neurofibromatosis • Oncology • Solid Tumor • BRAF • NF1

MEKMDM2: Early Phase Study Evaluating MEK and MDM2 Inhibition in Patients With NF1 and MPNST (clinicaltrials.gov) - P1/2 | N=45 | Not yet recruiting | Sponsor: AeRang Kim | Initiation date: Apr 2025 ➔ Oct 2025

Trial initiation date • Brain Cancer • Genetic Disorders • Neurofibromatosis • Neurofibrosarcoma • Sarcoma • Solid Tumor

A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma (clinicaltrials.gov) - P3 | N=165 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • Genetic Disorders • Glioma • Neurofibromatosis • Oncology • Solid Tumor • NF1

A transcriptomic, proteomic, and functional genetic atlas dissects neurofibromin function in the peripheral nervous system. (PubMed, Proc Natl Acad Sci U S A) - "NF1 mutation accordingly leads to Ras misactivation and downstream activation of RAF/MEK/ERK signaling, leading to the approval of the MEK inhibitor selumetinib for NF-1 associated peripheral nervous system (PNS) tumors...However, upstream sonof sevenless 1 inhibition shows limited efficacy in iPNs due to compensation by SOS2. Finally, proximal proteomics reveals Kirsten rat sarcoma virus (KRAS), but not Harvey rat sarcoma virus (HRAS) or neuroblastoma Ras viral oncogene homolog (NRAS), associates with neurofibromin in iPN cells, and pan-KRAS inhibition is sufficient to block ERK activation and CDK1/2 activation in NF1 mutant cells, suggesting blocking KRAS may be a therapeutic approach for NF1 mutant PNS tumors."

Journal • Genetic Disorders • Neuroblastoma • Neurofibromatosis • Oncology • Sarcoma • Solid Tumor • CDK1 • HRAS • KRAS • NF1 • NRAS • PTPN11

Combined oncogene and pyruvate dehydrogenase kinase inhibition enhances tumor response in resistant NSCLC cells (EACR 2025) - "In parallel, dichloroacetate (DCA), a small molecule that alters cancer cell metabolism by inhibiting pyruvate dehydrogenase kinase (PDK), has been investigated for its potential to reverse the Warburg effect and reprogram tumor cell metabolism...Consequently, EGFR-mutant H1975, c-MET amplified H1993 and KRAS-mutant A549 NSCLC cells, were treated with TKIs (osimertinib, crizotinib and selumetinib, respectively), DCA alone or in combination with TKIs (halved dose)... Our findings indicate that the combination of TKIs and DCA, at low doses, represents a promising therapeutic approach to overcome resistance and improve clinical outcomes in target cancer therapy."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL2L11 • EGFR • KRAS • MET