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

Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma (clinicaltrials.gov) - P1/2 | N=217 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2026 ➔ Mar 2027 | Trial primary completion date: Jul 2026 ➔ Jan 2026

Trial completion date • Trial primary completion date • Astrocytoma • Brain Cancer • Genetic Disorders • Glioma • Neurofibromatosis • Oncology • Pediatrics • Pilocytic Astrocytoma • Solid Tumor • BRAF • KIAA1549

HISTONE INDUCED ENDOTHELIAL DYSFUNCTION IN SEPTIC ACUTE KIDNEY INJURY VIA TLR 4-EPAC 1-MEK-ERK PATHWAY (ISN-WCN 2026) - "The compounds TAK-242, Forskolin, ESI-09, and selumetinib were employed to modulate the activation of TLR4, EPAC1, and MEK, respectively. In vivo, inhibition of TLR4 or MEK activation, or enhancement of EPAC1 expression, attenuated vascular permeability, mitigated multiple organ injury, and improved survival outcomes in sepsis.Download: Download high-res image (1MB)Download: Download full-size imageDownload: Download high-res image (1MB)Download: Download full-size imageDownload: Download high-res image (700KB)Download: Download full-size imageDownload: Download high-res image (1MB)Download: Download full-size imageDownload: Download high-res image (765KB)Download: Download full-size imageDownload: Download high-res image (938KB)Download: Download full-size imageConclusion Our findings reveal that the metabolic cross-talk between chromatin-derived histones and the endothelium plays a critical role in the pathophysiology of sepsis. Inhibition of the TLR4-EPAC-MEK-ERK..."

Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock • CDH5 • IL1B • IL6 • LCN2 • TLR4 • TNFA

Real-world outcomes for selumetinib in pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas in Japan: A 1-year interim analysis. (PubMed, Neurooncol Adv) - "The safety profile of selumetinib was generally consistent with the findings of the phase 2 SPRINT trial and Japanese phase 1 trial. No new safety concerns were identified."

Journal • Real-world evidence • Dermatitis • Dermatology • Genetic Disorders • Immunology • Neurofibromatosis • Pediatrics • Solid Tumor • NF1

Vertical MAPK pathway targeting is required for tumor regression in novel human and mouse models of NF1-inactivated melanoma (AACR 2026) - "While the MEK inhibitor selumetinib has been FDA approved for pediatric patients with Neurofibromatosis type 1 with benign plexiform neurofibromas arising from germline NF1 mutation, MEK inhibitors and other therapies targeting the MAPK pathway have had limited clinical benefit in patients with tumors driven by NF1-inactivation...As anticipated, loss of Nf1 conditioned the response to treatment with a BRAF monomer inhibitor (vemurafenib). While Nf1-inactivated cells were more sensitive to MEK inhibition (trametinib), or combined BRAF/MEK inhibition, as seen by suppression of ERK phosphorylation (pERK), cyclin D1 and DUSP6 expression, and cell proliferation, levels of pERK quickly rebounded. BRAF V600E/NF1/TP53-mutant cells were also transiently sensitive to combined inhibition of BRAF and the positive RAS adaptor SHP2 (using SHP099); with the rebound of pERK mitigated only by MEK, not upstream BRAF/SHP2, inhibition. In mice with established BrafCA/Nf1/Trp53-null tumors..."

Preclinical • Brain Cancer • Glioma • Melanoma • Oncology • Solid Tumor • CCND1 • DUSP6 • NF1

Decoding the tumor microenvironment of NF1 tumors using spatial and cell-type specific analyses of patient-derived organoids (AACR 2026) - "Current therapies for NF1 associated tumors are extremely limited, being the MEK 1/2 inhibitors selumetinib and mirdametinib the only FDA-approved drugs for patients with symptomatic inoperable pNFs. This methodology will be coupled with our high throughput mini-ring organoid screening platform (Phan et al, Communications Biology 2019; Al Shihabi et al, Science Advances 2022), to rapidly screen FDA-approved drugs, along with a modified 3D-compatible Cell Painting assay for providing unbiased phenotypic readouts of the impact of therapeutic agents on each cell type as well as proteomics approaches. By integrating these methods, we aim to address the challenges posed by the cellular heterogeneity of NF1-associated tumors and to identify precision therapeutic strategies for NF1 patients."

Biomarker • Clinical • Tumor microenvironment • Brain Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • MAP2K1 • NF1

Immunogenic eradication of melanoma via ultrasmall lactoferrin-ICD inducer nanoconjugates integrated with BRAF-inhibitory liposomes (AACR 2026) - "First, we engineered liposomes encapsulating dabrafenib (DFN, BRAF inhibitor) and selumetinib (SLM, MEK inhibitor)...Second, we synthesized ultrasmall lactoferrin (LF) nanoconjugates with ICD inducer drugs including doxorubicin (DOX), shikonin and bortezomib via a pH-responsive hydrazone bond to induce ICD of melanoma cells...The intravenously injected nanomedicine markedly increased the antitumor efficacy with significant reduction of tumor volume relative to vehicle treated group and mice treated with αPDL1 alone. In conclusion, the combined delivery of BRAF inhibitory and ICD inducing nanomedicine into one platform could boost the antitumor immune response to αPDL1 therapy and hence overcome the immune resistance of melanoma cells."

IO biomarker • Melanoma • Oncology • Solid Tumor • HMGB1

Adverse Events and Toxicity of Systemic Treatments for Uveal Melanoma: A Systematic Review. (PubMed, Cancers (Basel)) - "Analysis of treatment-related adverse events (TRAEs) of grade ≥3 showed that patient cohorts receiving trametinib, selumetinib, and darovasertib experienced the lowest incidence of severe events (with the exception of creatine phosphokinase elevation observed with selumetinib), suggesting a comparatively more favorable safety profile for these agents. At present, the most robust efficacy data in the metastatic uveal melanoma setting are available for tebentafusp and darovasertib. This study provides the most comprehensive analysis of TRAEs in randomized trials of UM, delineating the toxicity and safety profiles of current therapies to guide personalized treatment decisions."

Adverse events • Journal • Review • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Trametinib and Fimepinostat Induce Malignant Peripheral Nerve Sheath Tumor Cell Death In Vitro. (PubMed, Cancers (Basel)) - "These studies demonstrate in vitro efficacy for two candidate MPNST therapeutics which could reduce tumor burden and metastasis in NF1 patients."

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

Prolonged Mitogen-Activated Protein Kinase Kinase (MEK) Inhibition Induces Increase in Proteolysis and Compensatory Phosphorylation of MEK and Protein Kinase B (AKT) in Plexiform Neurofibroma Cells. (PubMed, Cells) - "FDA-approved mitogen-activated protein kinase kinase (MEK) inhibitors, selumetinib and mirdametinib, have shown ~30% tumor shrinkage in 70% and 42% pNF1 patients, respectively. This response was also observed in MPNST cell lines treated with MEK inhibitors. These findings suggest that adaptive activation of upstream and parallel survival pathways may counteract the intended effects of MEK inhibition and support the rationale for combination strategies to improve therapeutic outcomes in NF1-associated tumors."

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

Complex symptomatic PN surgery in NF1: Outcomes and the necessity of subsequent selumetinib treatment (Sarcoma-RC 2026) - "Legal entity responsible for the study The authors. Funding Has not received any funding."

Surgery • Genetic Disorders • Hematological Disorders • Neurofibromatosis • Sarcoma • Solid Tumor • NF1

PASS of Paediatric Patients Initiating Selumetinib (clinicaltrials.gov) - P=N/A | N=124 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Neurofibromatosis • Pediatrics • Solid Tumor • NF1

NF113: Study of Cabozantinib With Selumetinib for Plexiform Neurofibromas (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Girish Dhall, MD | Trial completion date: Mar 2034 ➔ Aug 2034 | Trial primary completion date: Mar 2033 ➔ Aug 2033

Trial completion date • Trial primary completion date • Genetic Disorders • Neurofibromatosis • Solid Tumor • NF1

Mirdametinib in symptomatic neurofibromatosis type 1 plexiform neurofibromas. (PubMed, Expert Rev Anticancer Ther) - "Mirdametinib represents a meaningful advance in the management of NF1-PNs, offering durable tumor volume reduction, improvements in pain and quality of life, and a manageable safety profile across age groups. While head-to-head comparisons with other MEK inhibitors are lacking, available evidence suggests a favorable balance of efficacy and tolerability that may support its use as a first-line systemic option in appropriately selected patients."

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

Alexion, AstraZeneca Rare Disease’s Koselugo (selumetinib), an oral, selective MEK inhibitor, has been approved in Canada for the treatment of adult patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). (Canada Newswire) - "The approval by Health Canada was based on positive results from KOMET, the largest and only placebo-controlled global Phase III trial in this patient population. Data were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The Lancet."

Canada approval • Neurofibromatosis • Oncology

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Recruiting | Sponsor: UNICANCER | Trial completion date: Jun 2021 ➔ Dec 2022 | Trial primary completion date: Jun 2019 ➔ Dec 2021

IO biomarker • Trial completion date • Trial primary completion date

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Dec 2023 ➔ Dec 2024

IO biomarker • Trial completion date • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Dec 2022 ➔ Dec 2023

IO biomarker • Trial completion date • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Recruiting | Sponsor: UNICANCER | N=460 ➔ 1460 | Trial primary completion date: Oct 2016 ➔ Jun 2019

Enrollment change • IO biomarker • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=460 | Recruiting | Sponsor: UNICANCER

IO biomarker • New P2 trial • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Dec 2024 ➔ Dec 2025

IO biomarker • Trial completion date • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial primary completion date: Dec 2021 ➔ Dec 2022

IO biomarker • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor

108: Updates in the Management of BRAF and MEK Inhibitors in Pediatric Solid Tumors (HOPA 2026) - "This session will provide an overview of these new agents and formulations and their use in the pediatric population. UAN: 0465-0000-26-025-L01-P Knowledge or Application Based: Knowledge Learning Objectives: Evaluate recent literature exploring the use of selumetinib and trametinib/dabrafenib in pediatric solid tumorsDiscuss key clinical trials leading to the approval of mirdametinib and tovorafenib in the pediatric populationIdentify available dosage forms of BRAF/MEK pathway inhibitors and associated administration challenges in the pediatric populationDevelop strategies to monitor and manage adverse effects of BRAF/MEK pathway inhibitors in pediatric patients"

Clinical • Oncology • Pediatrics • Solid Tumor

CDK4/6 inhibitors in low-grade serous ovarian carcinoma (LGSOC): a pooled analysis (ESGO 2026) - "MEK inhibitors (trametinib [1], selumetinib [2]) provide limited activity, while smaller studies evaluated BRAF and PI3K inhibition [3, 4]. More recently, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have emerged as a promising strategy [5–7].Methodology A systematic search of MEDLINE, Embase, and ClinicalTrials.gov (2000–2025) identified phase I/II or basket studies evaluating palbociclib, ribociclib, or abemaciclib in LGSOC...The highest activity was observed with ribociclib + letrozole in Colon-Otero et al...2025 achieved ~ 20 % ORR, while no responses occurred in the ribociclib + spartalizumab cohort (Garrido-Castro 2025)...Reported toxicity was predominantly haematologic, consistent with the known CDK4/6-inhibitor profile.Conclusion Endocrine-based CDK4/6 inhibition shows meaningful and durable disease control in LGSOC, with benefit rates exceeding those achieved by chemotherapy. Evidence remains limited and heterogeneous; ongoing..."

Retrospective data • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

ESMART: European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (clinicaltrials.gov) - P1/2 | N=285 | Recruiting | Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

New P1/2 trial • Hematological Malignancies • Oncology • Pediatrics