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

Amedart will hold clinical trials of the first domestic biosimilar of Koselugo (GxP News) - "The Russian Ministry of Health has granted the Russian pharmaceutical company Amedart permission to conduct a comparative clinical trial on the bioavailability and bioequivalence of a generic version of the orphan drug Koselugo (selumetinib), which was originally developed by the Anglo-Swedish pharmaceutical company AstraZeneca. The information appeared in the State Register of Medicines. This drug is intended to treat neurofibromatosis type 1 in children...The trials of the reference drug will be carried out at the Tomsk National Research Medical Center of the Russian Academy of Sciences. The study will involve 40 healthy volunteers, and the completion of the clinical trial is scheduled for the end of 2027."

New trial • Neurofibromatosis

Olaparib in Combination With Either Durvalumab, Selumetinib, or Capivasertib or Ceralasertib Alone in Treating Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P2 | N=27 | Terminated | Sponsor: Gordon Mills, MD, PhD | Trial completion date: Nov 2025 ➔ Dec 2024 | Active, not recruiting ➔ Terminated; loss of funding

Monotherapy • Trial completion date • Trial termination • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • ER • HER-2 • PGR

PLINABULIN AND SELUMETINIB INDUCE AAMS REPROGRAMMING INTO M1-LIKE MACROPHAGES AND REDUCE AML CELL VIABILITY (EHA 2025) - "We then evaluated gene expression changes under the combination treatment of AZD6244 and revumenib (a Menin inhibitor) to assess AAM repolarization. In conclusion, we found that BPI-2358 and AZD6244 can reprogram AAMs into M1-like macrophages, enhancing their pro-inflammatory features and phagocytic capacity while reducing AAM-CD163⁺ levels and AML viability, representing a promising therapeutic approach in combination with targeted therapies in AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD163 • CD34 • CD80 • KIT • MN1 • MRC1 • NOS2 • TNFA

Motherwort synergized with oxytocin for postpartum hemorrhage prevention: Integrated clinical efficacy and mechanism exploration. (PubMed, Phytomedicine) - "Our study, from clinical phenomena to mechanism validation, demonstrates that the combined regimen of motherwort injection and oxytocin exhibits superior efficacy in preventing PPH compared to oxytocin monotherapy. A key mechanistic insight is the activation of the MAPK signaling pathway, which underpins the synergistic action of motherwort injection with oxytocin in enhancing uterine contraction. These findings highlight the therapeutic potential of integrating traditional Chinese medicine (motherwort injection) with Western medicine (oxytocin) for improved PPH management."

Journal • Hematological Disorders • Obstetrics • Postpartum Hemorrhage • MAP2K1

Molecular profiling in targeted therapy of gliomas in a community setting. (ASCO 2025) - "Accordingly, 11 patients received targeted therapy: 3 patients olaparib (RAD51C, BRCA2, H3.3 G34), 2 pembrolizumab (TMB high), 1 ivosidenib (IDH1), 1 selumetinib (NF1), 1 alpelisib (PIK3CA), 1 erdafitinib (FGFR3), 1 trametinib (NF1) and 1 dabrafenib/trametinib (BRAF) and then everolimus (TSC2). Molecular profiling nowadays is not only mandatory in glioma classification but can also provide additional therapies in patients with limited options."

IO biomarker • Tumor mutational burden • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • High Grade Glioma • Oligodendroglioma • Oncology • Solid Tumor • ATRX • BRAF • BRCA2 • EGFR • FGFR3 • IDH1 • MSI • NF1 • PD-L1 • PIK3CA • PTEN • RAD51C • TERT • TMB • TP53 • TSC2

A telomere-associated molecular landscape reveals immunological, microbial, and therapeutic heterogeneity in colorectal cancer. (PubMed, Front Mol Biosci) - "From a therapeutic standpoint, high TELscore tumors exhibited reduced sensitivity to standard chemotherapeutic agents-including Fluorouracil, Irinotecan, Oxaliplatin, and Docetaxel-as reflected by elevated IC50 values. Conversely, these tumors demonstrated increased susceptibility to MAPK pathway inhibitors, such as Selumetinib and Trametinib...TELscore is a robust stratification tool that captures the interplay between tumor biology, immune characteristics, and microbial ecology in colorectal cancer. By identifying clinically relevant subtypes with distinct therapeutic vulnerabilities, TELscore offers a powerful framework to advance personalized treatment and precision oncology."

Heterogeneity • IO biomarker • Journal • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Immune Modulation • Immunology • Oncology • Solid Tumor

Trial of Selumetinib and Bromodomain Inhibitor With Durvalumab for Sarcomas (clinicaltrials.gov) - P2 | N=41 | Not yet recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Jun 2031 ➔ Dec 2031 | Trial primary completion date: Jun 2030 ➔ Dec 2030

Trial completion date • Trial primary completion date • Brain Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor

NF114: Selumetinib for the Prevention of Plexiform Neurofibroma Growth in NF Type 1 (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Jun 2032 ➔ Sep 2032 | Trial primary completion date: Jun 2031 ➔ Sep 2031

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

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

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

Unexplored targets in myeloid neoplasms: Investigating potential areas of clinical actionability using a comprehensive genomic database. (ASCO 2025) - "Our findings identify actionable mutations in MNs (KRAS, EZH2, NF1, BRAF) with FDA-approved targeted therapies (e.g. sotorasib, tazemetostat, selumetinib, vemurafenib). These mutations are underexplored in MNs, though some studies have assessed MEK inhibitors for certain subtypes."

Clinical • Genomic data • Hematological Malignancies • Oncology • Solid Tumor • BRAF • BRCA2 • EGFR • EZH2 • KRAS • NF1 • NRAS • NTRK1 • RET • ROS1

Perfume trial: Phase II trial of binimetinib in patients with BRAF fusion-positive low-grade glioma or pancreatic cancer. (ASCO 2025) - P2 | "Recently, tovorafenib has been granted accelerated approval by the FDA for pediatric low-grade glioma (LGG) with BRAF alteration (including BRAF fusion)...Phase I/II trials with selumetinib or binimetinib have shown efficacy in patients with BRAF fusion-positive LGG...Enrollment started in March 2023 and is ongoing at 6 facilities in Japan. As of Dec 2024, 6 patients with LGG and 3 patients with PC were enrolled (Clinical trial information: jRCT2031230007, NCT06159478)."

Clinical • P2 data • Astrocytoma • Brain Cancer • CNS Tumor • Glioma • Oncology • Pancreatic Cancer • Pediatrics • Pilocytic Astrocytoma • Solid Tumor • BRAF

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 | "In the first international, randomized, placebo-controlled trial in adults with NF1-PN, SELU achieved a significant ORR vs PBO (C16), meeting the primary endpoint, and a clinically meaningful reduction in PN-associated chronic pain (C12)."

Clinical • P3 data • Dermatitis • Dermatology • Fatigue • Genetic Disorders • Immunology • Infectious Disease • Neurofibromatosis • Novel Coronavirus Disease • Pain • Rare Diseases • Solid Tumor • NF1

“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 and labelling of Koselugo capsules and Koselugo granules in capsules for opening." (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 7 – 10 Apr 2025

PRAC • Neurofibromatosis • Oncology

Development of two different eco-friendly label-free platforms for analysis of selumetinib. (PubMed, Acta Pharm) - "The HPLC-PDA involved chromatographic separation of SEL and tozasertib (TOZ), internal standard, on a C18 column both were detected at 255 nm. Eco-friendliness assessment confirmed the adherence of both platforms to green analytical approaches. MW-UV and HPLC-PDA are simple and fast, enabling high-throughput analysis, thus introducing valuable tools for routine use in quality control and clinical laboratories for SEL quantification."

Journal • Genetic Disorders • Neurofibromatosis • Pediatrics • Solid Tumor

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

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

National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=423 | Active, not recruiting | Sponsor: University of Birmingham | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

IO biomarker • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • NKX2-1 • TP63

Risk Assessment for Biopharmaceutics Classification System Class IV Molecule Containing Immediate Release Products: Use of In-Silico Prediction Tools and Physiologically Based Pharmacokinetic Modeling. (PubMed, AAPS J) - "This tool was used to predict the carcinogenic potential of 37 BCS IV molecules and further clinical exposure risk assessment was conducted on identified 5 high risk category molecules namely edoxaban, selumetinib, bosutinib, furosemide, hydrochlorothiazide where transporters are involved in absorption. The PBPK models were used to evaluate the impact of altered permeability and transporter kinetics on exposures, that may happen in presence of antioxidants. Further, the impact of permeability within ± 10-20% was evaluated on clinical exposures to determine permeability safe space (region within which bioequivalence is guaranteed as compared to the target formulation)."

Journal • PK/PD data

A new medicine has been approved that treats inoperable plexiform neurofibromas in children (GMA News) - "The Philippine Food and Drug Administration approves a game-changing prescription medicine, Selumetinib. The new drug is for 'the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in children and teens with Neurofibromatosis type 1 (NF1)'."

Approval • Neurofibromatosis

Severe cervical kyphosis in a complex child with NF1, case report and literature review. (PubMed, Childs Nerv Syst) - "Combined anterior and posterior fusion (CAP) is generally the best treatment option, although it is not always feasible. When plexiform, symptomatic, inoperable neurofibromas coexist, surgery can be preceded or followed by MEK inhibitor treatment for better control or a volumetric reduction of the tumors. The best therapeutic choice should always be the result of a multidisciplinary, expert approach and patient-tailored design."

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

Assessment of Conditional Listing for Highly Uncertain and High-Priced Drugs in Taiwan (ISPOR 2025) - " 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."

Balancing the Burden: Comparing Treatment Burden of IV vs. Oral Therapy in Pediatric Brain Tumors (ASPHO 2025) - " Intravenous (IV) therapy (carboplatin/vincristine and cisplatin/cyclophosphamide/ etoposide/vincristine) was associated with more total adverse events (n = 39) compared to oral therapy (larotrectinib, selumetinib, trametinib/dabrafenib, n = 20) and combination IV and oral therapy (vinblastine and selumetinib, n = 15). Physicians need to recognize the differences in treatment burdens between IV and oral therapies for pediatric brain tumor patients. Our findings revealed that IV therapy was associated with a higher number of adverse events, especially gastrointestinal events, and increased healthcare utilization, including more frequent clinic visits, compared to oral therapies. Further research is needed to evaluate the efficacy of oral treatment compared with IV therapy."

Clinical • Brain Cancer • Gastrointestinal Disorder • Glioma • Oncology • Pediatrics • 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) | N=2316 ➔ 1376 | Trial completion date: Jun 2025 ➔ May 2026 | Trial primary completion date: Jun 2025 ➔ Mar 2025

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

Selumetinib for Blood Pressure Control in Patients With Neurofibroatosis-1 and Mid-Aortic Syndrome (ASPHO 2025) - "Hypertension was refractory to treatment with clonidine, amlodipine, and enalapril, and she was subsequently started on Selumetinib 20mg twice daily. Selumetinib has proven to be effective in decreasing the size of plexiform neurofibromas, and its role as a MEK inhibitor shows promise in halting arterial remodeling that contributes to renovascular hypertension. These cases highlight the potential for Selumetinib in the management of hypertension in NF1 associated plexiform neurofibromas and mid-aortic syndrome."

Clinical • Cardiovascular • Genetic Disorders • Hypertension • Neurofibromatosis • Oncology • Solid Tumor • NF1

Inhibition of MCL-1 and MEK overcomes MEK inhibitor resistance in triple-negative and inflammatory breast cancers. (PubMed, Mol Cancer Ther) - "In an in vivo mouse model, inhibition of MCL-1 restored sensitivity to AZD6244. Our results suggest that MCL-1 is a driver of MEKi resistance and that combining an MCL-1i with a MEKi warrants further investigation in triple-negative and triple-negative inflammatory breast cancer."

Journal • Breast Cancer • Hematological Malignancies • Inflammatory Breast Cancer • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer