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

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

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) (clinicaltrials.gov) - P2 | N=1376 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2026 ➔ Jan 2027

Biomarker • Trial completion date • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Ewing Sarcoma • Germ Cell Tumors • Glioma • Hematological Malignancies • Hepatoblastoma • High Grade Glioma • Langerhans Cell Histiocytosis • Lymphoma • Medulloblastoma • Nephrology • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Osteosarcoma • Pediatrics • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • BRAF

Fatal Pericarditis and Cardiac Tamponade During Selumetinib Treatment for Pericardial Neurofibroma. (PubMed, J Dermatol) - No abstract available

Journal • Cardiovascular • Neurofibromatosis • Solid Tumor

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

Pharmacokinetics and Safety of Selumetinib Granule Formulation in Children With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas (SPRINKLE; phase I/II). (PubMed, J Clin Oncol) - P1/2 | "Selumetinib granule formulation (25 mg/m2 dose equivalent, twice a day) had comparable exposure to selumetinib capsule formulation, and was palatable with a manageable safety profile. Selumetinib granule formulation is potentially suitable for young children with NF1-PN who cannot swallow capsules."

Journal • P1/2 data • PK/PD data • Genetic Disorders • Neurofibromatosis • Pediatrics • Solid Tumor • NF1

The SPRINKLE phase 1/2 clinical trial (NCT05309668) evaluated a novel granule formulation of selumetinib (Koselugo), a potent MEK1/2 inhibitor, for pediatric patients with neurofibromatosis type 1-related plexiform neurofibromas (NF1-PN) who are unable to swallow capsules. (Targeted Oncology) - "The study successfully met its primary end points, demonstrating that the granule formulation (at a 25 mg/m² twice-daily dose) provides drug exposure comparable with the established capsule formulation in the pivotal SPRINT (NCT01362803) study...Comparability was established if the 95% confidence intervals (CIs) of the granule formulation's geometric mean area under the curve (AUC₀₋₁₂) fell within a predefined acceptance range (60%-140%) of the SPRINT study's value (2,009 h·ng/mL)...Key findings also indicate a manageable safety profile consistent with previous selumetinib studies and the known safety profile of the capsule formulation, with most adverse events (AEs) being mild to moderate (grade 1 or 2) and none leading to treatment discontinuation or dose reduction."

P1/2 data • Neurofibromatosis • 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

Integrating cuproptosis- and ferroptosis-related gene signatures to predict prognosis, immunotherapy response, and drug sensitivity in patients with skin cutaneous melanoma. (PubMed, Front Immunol) - "IFNG, PTPN6, SLC38A1, and SOCS1 may serve as potential biomarkers of poor prognosis in SKCM patients. These genes demonstrate predictive value for immunotherapy response and drug sensitivity, particularly indicating susceptibility to selumetinib treatment, and therefore show substantial potential for clinical translation."

Biomarker • Gene Signature • IO biomarker • Journal • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • IFNG • SOCS1

Pediatric-Friendly Formulations: Critical to Maximizing Benefit of Novel Therapeutics Such as Selumetinib for Children With Neurofibromatosis and Other Neoplasms. (PubMed, J Clin Oncol) - No abstract available

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

Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis. (PubMed, Sci Adv) - "Pharmacological inhibition of FAK with single agent VS-4718 did not significantly reduce macroscopic tumor volume; however, its use in combination with the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib resulted in both a significant reduction in tumor volume and the preservation of dorsal root ganglion architecture. Our findings establish a critical role for FAK in schwannoma development and provide rationale for evaluation of combination FAK plus MEK inhibition in future clinical trials for NF2-associated SWN."

Journal • Preclinical • Brain Cancer • Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor • HGF • NF2 • NLRC5 • PTK2

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

TATTON: AZD9291 in Combination With Ascending Doses of Novel Therapeutics (clinicaltrials.gov) - P1 | N=344 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2025 ➔ Dec 2026

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

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

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 completion date: Jun 2026 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

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

Antibody-mediated blockade of gremlin-1 in combination with gemcitabine or MEK inhibition in a genetically engineered mouse model of pancreatic cancer. (ASCO-GI 2026) - " We used a genetically engineered mouse model of pancreatic cancer to evaluate the therapeutic effect of antibody-mediated inhibition of gremlin-1 (Ab7326) alone, or in combination with gemcitabine or a MEK 1/2 inhibitor (selumetinib or UCB-554). Blocking gremlin-1 in combination with gemcitabine or MEK inhibition may have benefit in the treatment of pancreatic cancer. Ginisortamab is now in a Phase 2 clinical trial in patients with PDAC."

Combination therapy • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS • MAP2K1 • PDX1

108: Updates on the Use and 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. 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

SARC031: A Phase 2 Trial of Selumetinib and Sirolimus for Patients with Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumors (MPNST). (PubMed, Clin Cancer Res) - "The combination was safe with manageable and expected AEs, but did not meet study parameters for further evaluation in MPNST. Correlative studies were informative and may guide future therapeutic trials of MPNST."

Journal • P2 data • Brain Cancer • Dyslipidemia • Hypertriglyceridemia • Mucositis • Neurofibrosarcoma • Oncology • Pain • Sarcoma • NF1

Selumetinib and Azacitidine in High Risk Chronic Blood Cancers (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: University of Chicago | Trial completion date: Sep 2025 ➔ Sep 2027 | Trial primary completion date: Sep 2025 ➔ Sep 2027

Trial completion date • Trial primary completion date • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology

Targeted therapies in optic pathway gliomas. (PubMed, Cancer Treat Rev) - "Targeted therapies constitute a potentially paradigm-shifting development in the management of OPGs, enhancing disease control while improving the prospects for long-term visual preservation. This review underscores the need for individualized, biomarker-driven approaches and highlights challenges including resistance, long-term safety, and therapy duration."

Journal • Review • Brain Cancer • Genetic Disorders • Glioma • Neurofibromatosis • Oncology • Solid Tumor • NF1

MEK Inhibition Reduces Vascular Malformations and Gene Dysregulation in NRASQ61R Human Endothelial Cells. (PubMed, Pediatr Blood Cancer) - "Trametinib was the most effective MEK inhibitor, correcting some dysregulated genes in NRASQ61R ECs, including some in the Notch pathway. Trametinib reduced vessel overgrowth in xenografts of NRASQ61R ECs. These studies support using trametinib treatment for KLA patients with an NRASQ61R mutation."

Journal • HES1 • JAG1 • NOTCH1 • NRAS

Koselugo: Newly added patents in Orange Book (Orange Book) - Expiry on Dec 12, 2026 and Mar 13, 2028

Patent • Genetic Disorders • Neurofibromatosis • Oncology • Rare Diseases

Real-World Treatment Study of Koselugo (Selumetinib) (clinicaltrials.gov) - P=N/A | N=200 | Recruiting | Sponsor: AstraZeneca | N=150 ➔ 200

Enrollment change • HEOR • Real-world evidence • Genetic Disorders • Neurofibromatosis • Solid Tumor

Transcriptome-guided drug repurposing identifies selumetinib for an aggressive epithelial cancer. (PubMed, J Invest Dermatol) - "RNA sequencing identified early growth response protein 1 (EGR1), fos proto-oncogene (FOS), and dual-specificity phosphatase 6 (DUSP6) as candidate biomarkers of treatment response. Selumetinib, identified by computational drug screening, demonstrates efficacy against RDEB-SCCs in vitro and in vivo, suggesting its potential for clinical use."

IO biomarker • Journal • Oncology • Squamous Cell Carcinoma • CDH1 • DUSP6 • EGR1 • PD-L1 • VIM

SPRINKLE: Pharmacokinetics, Safety and Efficacy of the Selumetinib Granule Formulation in Children Aged ≥1 to <7 Years With NF1-related Symptomatic, Inoperable PN (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: AstraZeneca | Trial primary completion date: Apr 2024 ➔ Nov 2027

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