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

Challenges of Selumetinib Therapy for Neurofibromatosis in a Resource-Limited Setting. (PubMed, Cureus) - "This case highlights the efficacy of selumetinib in NF1-associated PNs and the consequences of treatment interruption. It underscores the need for reliable access to targeted therapies in resource-limited settings to ensure sustained clinical benefit."

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

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

Assessment of Conditional Listing for Highly Uncertain and High-Priced Drugs in Taiwan (ISPOR 2025) - "The review and assessment process were conducted independently by two researchers. A total of 12 drugs were considered for conditional listing between 2022 and 2024, which included Pemazyre, Tepmetko, Qarziba, Kymriah, Vitrakvi, Blincyto, Vydamax, Takhzyro, Polivy, Velexbru, Spevigo, and Koselugo. The conditional listing opens up new opportunities for high-priced drugs. However, the 2-year real-world evidence for Pemazyre remains insufficient for the government to make a final reimbursement decision. Consequently, the results of the HTA will pose challenges in the future in Taiwan."

Dual inhibition of PIKfyve and KRAS/MAPK targets metabolic vulnerabilities of pancreatic ductal adenocarcinoma (AACR 2025) - "Notably, all but one mouse were cured when treated with both ESK981 and MEK inhibitor trametinib. To evaluate the significance of PIKfyve in PDAC, we employed RNA-ISH and found that PIKfyve was significantly higher expressed in PDAC tissue compared to normal surrounding cells. Performing viability screens across multiple PDAC cell lines, we observed that they were highly sensitive to PIKfyve inhibitors apilimod and ESK981. This data suggested that PIKfyve is crucial for PDAC development.We then performed a metabolism-focused CRISPR screen with the selective pressure of PIKfyve inhibition to assess the metabolic role of PIKfyve in PDAC."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • ACACA • FAS • FASN • KRAS

Preclinical efficacy of the combination of MEK inhibitor plus KRAS G12D inhibitor for non-small cell lung cancer with KRAS G12D (AACR 2025) - "Although no phosphorylation of receptor tyrosine kinases that could be combination drug candidates were observed, several MEK inhibitors, such as trametinib, selumetinib and binmetinib, enhanced the efficacy of MRTX1133 in cell viability assays. The combination of trametinib with MRTX1133 suppressed tumor growth compared to MRTX1133 monotherapy with tolerable toxicity in KRAS G12D-mutated NSCLC in vivo models. In conclusion, our findings indicate that the preclinical efficacy of MRTX1133 monotherapy was limited for NSCLC with KRAS G12D, and therapeutic potential of MEK inhibitors in combination with MRTX1133."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

EGF-upregulated ESSENCE promotes colorectal cancer growth through stabilizing CAD and ferroptosis defense [WITHDRAWN] (AACR 2025) - "Our findings demonstrate the crucial role of ESSENCE in mediating CRC progression by regulating CAD stabilization and ferroptosis defense. Synergistically targeting MEK and inducting ferroptosis represents a promising therapeutic strategy for ESSENCE-high expression CRC."

Colorectal Cancer • Oncology • Solid Tumor • EGR1 • KEAP1

The RXR agonist MSU-42011 and the MEK inhibitor selumetinib reduce tumor burden by decreasing pERK levels and modulating immune cell populations within the NF1 tumor microenvironment (AACR 2025) - "The combination of MSU42011 and selumetinib also significantly reduced tumor growth and reduced pERK levels and tumor-promoting CD206+ macrophages in both a LL2 model of lung cancer driven by an activating Kras mutation and a syngeneic mouse model of MPNST. Based on the similarities in RAS activation and immune cell infiltration in NF1 and lung cancer, our next step is to confirm the immunomodulatory and anti-tumor effects of MSU-42011 and selumetinib in a genetically engineered model of PNF and MPNST."

Biomarker • Clinical • Immune cell • Tumor microenvironment • Brain Cancer • Lung Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • CCL2 • GLI2 • IL6 • KRAS • MRC1 • NF1 • PERK • TNFA

Targeting PARP to enhance sensitivity to MEK inhibitors in low-grade serous ovarian cancer (AACR 2025) - "MEK inhibitors, such as trametinib and selumetinib, hold therapeutic potential, but their efficacy is often limited by inherent or acquired resistance linked to dysregulated lipid metabolism and ferroptosis. In conclusion, treatment with the PARP inhibitor olaparib substantially enhances the efficacy of MEK inhibition in LGSOC by inducing ferroptosis, with synergy between olaparib and trametinib. This approach offers a promising strategy to extend clinical benefits, potentially address treatment resistance, and broaden the therapeutic landscape for LGSOC patients with limited options."

Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • AMHR2 • FTO • GPX4 • KRAS • NRAS • SLC7A11 • VIM • WTAP

In vivo, ex vivo, and in vitro (2D and 3D) tumor models: Uses, strengths and limitations (AACR 2025) - "The 138582-377-R Merkel cell (PDX) treated with cediranib (6 mg/kg) & erlotinib (90 mg/kg) Q5D for 3 wks resulted in 80% decrease in tumor vol compared with controls & 80% cytotoxicity in complex spheroids from the same tumor. Less than 90% cytotoxicity was achieved in the complex spheroids in the estimated clinical Cmax concentration range of entinostat. The combination of ipatasertib (60 mg/kg) & selumetinib (20 mg/kg) administered twice per day for 2-rounds of 10 days was less effective in the 171881-019-R breast ca PDX and the 845751-090-R head & neck squamous ca PDX than would be predicted by the complex spheroid studies."

Preclinical • Oncology • Solid Tumor

Specific drugs for rare diseases in a province of eastern China under catalog management: from 2021 to 2023. (PubMed, Front Pharmacol) - "Spesolimab, Sodium Phenylbutyrate, Nitisinone and Emapalumab are currently in short supply, and the delivery rate of 16 drugs such as Selumetinib, Sirolimus (tablet), Octreotide, Dimethyl Fumarate and Lanreotide is below 80%...This indicates a generally high level of accessibility to drugs for rare diseases in China. However, attention should be given to improving the supply capacity for drugs that are in short supply and have a low delivery rate."

Journal • Rare Diseases

Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibroma (PN): Primary analysis of KOMET (NCT04924608), a phase 3, international, randomized, placebo-controlled study. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT04924608 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • P3 data • Genetic Disorders • Neurofibromatosis • Solid Tumor • NF1

SEL-TH-1601: Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors (clinicaltrials.gov) - P2 | N=10 | Terminated | Sponsor: Children's Hospital Medical Center, Cincinnati | Completed ➔ Terminated; Results review of patient data

Trial termination • Brain Cancer • CNS Tumor • Ependymoma • Genetic Disorders • Glioma • Meningioma • Neurofibromatosis • Oncology • Solid Tumor • NF2

A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma (clinicaltrials.gov) - P3 | N=165 | Recruiting | Sponsor: National Cancer Institute (NCI) | N=290 ➔ 165

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

Mirdametinib (Gomekli) for neurofibromatosis type 1. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Genetic Disorders • Neurofibromatosis • Solid Tumor

A Phase 2 PBTC Study of Selumetinib for Recurrent/Progressive Pediatric Low-Grade Glioma: Strata 2, 5, and 6 with Long-term Outcomes on Strata 1, 3, and 4. (PubMed, Neuro Oncol) - "Selumetinib provided stability and responses across many pLGG subgroups, and some patients achieved prolonged disease control without additional therapy."

Journal • P2 data • Astrocytoma • Brain Cancer • CNS Tumor • Genetic Disorders • Glioma • Neurofibromatosis • Oncology • Pediatrics • Pilocytic Astrocytoma • Solid Tumor • BRAF • KIAA1549 • NF1

Ultrasound-Assisted Synthesis of Substituted Chalcone-Linked 1,2,3-Triazole Derivatives as Antiproliferative Agents: In Vitro Antitumor Activity and Molecular Docking Studies. (PubMed, Int J Mol Sci) - "Additionally, in the cell lines where activity was observed, some compounds demonstrated an In vitro inhibitory effect superior to that of the control, paclitaxel...In Gb-d1 cells, compounds 4l and 4p exhibited favorable interactions with mitogen-activated protein kinase (MEK) protein, similar to those observed with the known inhibitor selumetinib. In HeLa cells, compounds 4h and 4g showed activity against dihydrofolate reductase (DHFR) protein, driven by hydrogen bonding interactions and favorable aromatic ring orientations. On the other hand, compounds 4b and 4t exhibited no activity, likely due to unfavorable interactions related to halogen substitutions in the aromatic rings."

Journal • Preclinical • Brain Cancer • Cervical Cancer • CNS Tumor • Gallbladder Cancer • Glioblastoma • Hematological Malignancies • Hepatology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • DHFR • TGM2

NF113: Study of Cabozantinib With Selumetinib for Plexiform Neurofibromas (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Girish Dhall, MD | Trial completion date: Apr 2033 ➔ Jul 2033 | Initiation date: Apr 2025 ➔ Jul 2025 | Trial primary completion date: Apr 2032 ➔ Jul 2032

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

BISCAY: Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P1 | N=117 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2025 ➔ Jan 2026

Biomarker • Trial completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CCNE1 • CDKN2A • HRD • MYCL • MYCN • RB1

Novel Therapies for Neurofibromatosis Type 1-Associated Inoperable Plexiform Neurofibromas: A Systematic Literature Review (ISPOR 2025) - "These reported on a total of 21 unique studies on 11 emerging therapies: 6 MEK inhibitors (selumetinib, mirdametinib, trametinib, binimetinib, FCN-159, tunlametinib) and 5 targeted anti-cancer agents (cabozantinib, tipifarnib, sorafenib, sirolimus, everolimus)... The promising results of MEK inhibitors in therapeutic trials for NF1 demonstrate that targeting the MAPK/ERK pathway is an attractive therapeutic avenue for unresectable PNs. Because selumetinib is only approved for children, future reimbursement will require advanced studies establishing MEK inhibitor efficacy in adults."

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

“Extension of indication for KOSELUGO to include treatment of adults based on results from study D134BC00001 (KOMET)…as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated.” (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC)-Draft agenda for the meeting on 7 - 10 Apr 2025: “For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP”

PRAC • Neurofibromatosis • Oncology

“Extension application to introduce a new pharmaceutical form (Granules in capsules for opening) associated with new strengths (5 mg and 7.5 mg capsule) grouped with a Type II variation (C.I.4) to update sections 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC in order to align the SmPC...The Package Leaflet and Labelling are updated accordingly. The RMP version 3.1 has also been submitted.” (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC)-Draft agenda for the meeting on 7 - 10 Apr 2025: “For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP”

PRAC • Genetic Disorders • Neurofibromatosis • Rare Diseases

Exploration of SUSD3 in pan-cancer: studying its role, predictive analysis, and biological significance in various malignant tumors in humans. (PubMed, Front Immunol) - "Molecular docking studies revealed that selumetinib inhibits tumor cell proliferation...These findings provide valuable insights and establish a foundation for further exploration of SUSD3's role in pan-carcinomas. Additionally, they offer novel perspectives and potential targets for the development of innovative therapeutic strategies in cancer treatment."

Biomarker • IO biomarker • Journal • Pan tumor • Breast Cancer • Oncology • Solid Tumor • CD4

EGF-Upregulated lncRNA ESSENCE Promotes Colorectal Cancer Growth through Stabilizing CAD and Ferroptosis Defense. (PubMed, Research (Wash D C)) - "Importantly, combinational treatment of the mitogen-activated extracellular signal-regulated kinase inhibitor selumetinib and ferroptosis inducer sulfasalazine synergistically suppresses ESSENCE-high CRC in a patient-derived xenograft mouse model. Taken together, these findings demonstrate the crucial role of ESSENCE in mediating CRC progression by regulating CAD stabilization and suggest a therapeutic strategy of targeting the ESSENCE-CAD axis in CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • KEAP1

US Selumetinib Registry (clinicaltrials.gov) - P=N/A | N=37 | Terminated | Sponsor: Alexion Pharmaceuticals, Inc. | N=200 ➔ 37 | Trial completion date: Jun 2028 ➔ Nov 2024 | Recruiting ➔ Terminated | Trial primary completion date: Feb 2028 ➔ Nov 2024; Sponsor decision.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Genetic Disorders • Neurofibromatosis • Solid Tumor • NF1

A pan-cancer analysis reveals the oncogenic and immunological role of insulin-like growth factor 2 mRNA-binding protein family members. (PubMed, Discov Oncol) - "IGF2BPs exhibit significantly high expression in most tumors and are associated with prognosis, pathological stage, mutational status, methylation levels, and the relevant indicators of immunotherapy sensitivity in multiple tumors. Moreover, IGF2BPs may play an oncogenic role by activating common signaling pathways. Therefore, IGF2BPs may be potential prognostic markers for tumor therapy and targets for immunotherapy and drug therapy."

IO biomarker • Journal • Pan tumor • Tumor mutational burden • Microsatellite Instability • Oncology • AMPK • IGF2BP1 • MSI • TMB