Mepact (mifamurtide) / Medison, Takeda - LARVOL DELTA

Dragonfly: Evaluation of the Safety and Efficacy of Mifamurtide Versus Standard Treatment With Sorafenib in Patients With High-risk Osteosarcoma (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Anna Raciborska

New P2 trial • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Exploring New Frontiers in Osteosarcoma Treatment: Clinical Trial Insights. (PubMed, Recent Pat Anticancer Drug Discov) - "The necessity for integrated therapies combining immunotherapy, targeted delivery, and molecular insights to enhance OS treatment results is highlighted by developments in genomics and bone remodeling."

IO biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • TP53

RESPONSE TO MIFAMURTIDE AND TUMOR MICROENVIRONMENT: A DECONVOLUTION NANOSTRING ANALYSIS IN LOCALIZED OSTEOSARCOMA PATIENTS TREATED WITHIN THE ISG/OS2 CLINICAL TRIAL (CTOS 2024) - P2 | "Prognostic gene signatures derived from the tumor immune microenvironment have been identified for risk stratification of osteosarcoma pts, regardless of mifamurtide treatment. Importantly, we have also developed a mifamurtide-specific signature that predicts both OS and EFS. This promising tool might be used to select pts who could benefit from adjuvant mifamurtide.CIBERSORT analysis underscored that tumor immune infiltrate significantly affects prognosis in localized patients with osteosarcoma.CIBERSORT analysis allowed us to dissect the complex immune milieu of localized osteosarcoma and identify tumor-immune interactions possibly implicated in disease progression and treatment response.Prognostic gene signatures derived from the tumor immune microenvironment have been identified for risk stratification of osteosarcoma pts, regardless of mifamurtide treatment."

Biomarker • Clinical • Nanostring • Tumor microenvironment • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD8

Tumor immune microenvironment-associated prognostic and mifamurtide-response gene signatures for localized osteosarcoma: a correlative study of the ISG/OS2 trial. (PubMed, Clin Cancer Res) - "A validated osteosarcoma TME prognostic gene signature has been identified, regardless of mifamurtide treatment. Importantly, a mifamurtide-related signature was also developed. Tumor-immune interactions possibly implicated in disease progression and treatment response were shown."

Gene Signature • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD4 • CD8

Gut microbial DL-endopeptidase protects against alcohol-associated liver disease via hepatocyte NOD2 signaling. (PubMed, Free Radic Biol Med) - "Importantly, supplementation with a NOD2 ligand or its clinical analogue, mifamurtide, restored mitochondrial homeostasis and alleviated liver injury. Together, these findings identify the gut microbial DL-endopeptidase-NOD2 axis as a key protective mechanism against ethanol-induced liver injury and a promising therapeutic target in alcohol-associated liver disease."

Journal • Hepatology • Liver Failure • Metabolic Disorders

Understanding the molecular insights of marketed liposomal drugs using molecular dynamics simulations of reduced scale coarse-grained models. (PubMed, NPJ Drug Discov) - "In this study, we employed coarse-grained molecular dynamics simulation to investigate the structural details of the commercially available nine liposomal formulations, with five passive loading systems (Arikayce Kit®, Visudyne®, Ambisome®, Mepact®, and Exparel®) and four active loading systems (Doxil®, Myocet®, Onivyde®, and Vyxeos®)...In four active loading systems, the presence of ions within the liposome cavity promotes the self-aggregation of drugs, thereby enhancing drug retention and release profiles. This study provided valuable molecular insights for marketed liposomes formulation."

Journal

Mifamutide treatment plus chemotherapy results in pediatric osteosarcoma patients in Ankara University Medical School Department of Pediatric Oncology: A single center experience. (ASCO 2018) - "Doxorubicin, cisplatin, high-dose methotrexate with leucovorin rescue, and ifosfamide are well known chemotherapy agents.The immunomodulator mifamurtide (liposomal muramyl tripeptide phosphatidyl ethanolamine [L-MTP-PE]; activates macrophages and monocytes, has been safely given together with standard adjuvant chemotherapy in high-grade OS patients. Mifamurtide is generally well tolerated in pediatric OS patiens, with the majority of side effects reported as either mild or moderate, and it can be given in the out-patient setting. According to our preliminary results, mifamurtid has tendancy to reduce lung metastasis but data needs more follow up and more studies for confirmation."

Clinical • Sarcoma

ICONIC (Improving Outcomes Through Collaboration in Osteosarcoma): Insights from a national prospective cohort trial for newly diagnosed osteosarcoma patients. (ASCO 2026) - P | "In total, 229/253 (91%) pts receiving neoadjuvant treatment had methotrexate, doxorubicin, cisplatin (MAP); 259 underwent surgery, of which 52 (20%) had amputations; 101/161 (63%) of eligible pts received mifamurtide. ICONIC trial has identified variation in management and outcomes of OS, which will guide future practice and provided a successful platform for imaging and biomarker analysis, which is ongoing. Pt characteristics and outcomes according to age and primary site."

Clinical • Osteosarcoma • Sarcoma • Solid Tumor

SARCOME13: Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: UNICANCER | Trial primary completion date: Jan 2026 ➔ Sep 2026

Trial primary completion date • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

DRAGONFLY: Clinical trial (study) comparing the efficacy and safety of mifamurtide versus standard treatment containing sorafenib in pediatric and young adult patients with high-risk osteosarcoma (clinicaltrialsregister.eu) - P1/2 | N=40 | Not yet recruiting | Sponsor: Instytut Matki I Dziecka

New P1/2 trial • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor

Does mifamurtide affect the elimination of high-dose methotrexate in children with osteosarcoma? (PubMed, Cancer Chemother Pharmacol) - No abstract available

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

SARCOME13: Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (clinicaltrials.gov) - P2 | N=126 | Recruiting | Sponsor: UNICANCER | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

SARCOME13: Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (clinicaltrials.gov) - P2 | N=126 | Not yet recruiting | Sponsor: UNICANCER

New P2 trial • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

SARCOME13: Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: UNICANCER | Trial primary completion date: Sep 2025 ➔ Dec 2025

Trial primary completion date • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

SARCOME13: Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: UNICANCER | Trial primary completion date: Mar 2025 ➔ Sep 2025

Trial primary completion date • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

SARCOME13: Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: UNICANCER | Trial primary completion date: Oct 2024 ➔ Mar 2025

Trial primary completion date • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

SARCOME13: Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: UNICANCER | Recruiting ➔ Active, not recruiting | N=126 ➔ 60

Enrollment change • Enrollment closed • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

SARCOME13: Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (clinicaltrials.gov) - P2 | N=126 | Recruiting | Sponsor: UNICANCER | Trial completion date: Oct 2028 ➔ Oct 2033 | Trial primary completion date: Oct 2022 ➔ Oct 2024

Trial completion date • Trial primary completion date • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Reply to: Mifamurtide in Nonmetastatic High-Grade Osteosarcoma. (PubMed, J Clin Oncol) - No abstract available

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Mifamurtide in Nonmetastatic High-Grade Osteosarcoma. (PubMed, J Clin Oncol) - No abstract available

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

RETROSPECTIVE EVALUATION OF ACUTE AND CHRONIC CARDIOTOXICITY DUE TO ANTHRACYCLINES IN PEDIATRIC ONCOLOGY PATIENTS DIAGNOSED WITH LYMPHOMA AND SOLID TUMORS (SIOP 2025) - "Among the patients,31.7% (n=91) were diagnosed with lymphoma,while 68.2% (n=196) had a solid tumor.Mediastinal involvement was present in 29.3% of patients,and 9.4% had a history of mediastinal radiotherapy.The vast majority (98.2%) received only doxorubicin as part of their treatment.The overall incidence of cardiotoxicity was 14.6%(n=42),with 69.0% classified as acute,11.9% as early-onset chronic,and 19.1% as late-onset chronic cardiotoxicity.Tachycardia was the most common acute cardiotoxicity finding,and sinus tachycardia was the most frequent ECG abnormality.Cardiac biomarker positivity was detected in 10 patients.Among the five patients who developed early-onset chronic cardiotoxicity,one had a cumulative anthracycline dose of 450 mg/m².Nine patients developed late-onset chronic cardiotoxicity, with one patient reaching a cumulative dose of 480 mg/m².There was no significant difference in cardiotoxicity incidence concerning age, sex,or diagnosis of..."

Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Lymphoma • Oncology • Pediatrics • Solid Tumor

Micros: Tumor Microenvironment in Patients With Localized Osteosarcoma Treated With Mifamurtide: a Translational Study (clinicaltrials.gov) - P=N/A | N=80 | Completed | Sponsor: Istituto Ortopedico Rizzoli | Trial completion date: Jun 2025 ➔ Oct 2024 | Trial primary completion date: Jun 2025 ➔ Oct 2024 | Recruiting ➔ Completed

Biomarker • Trial completion • Trial completion date • Trial primary completion date • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • PD-L1

The benefits of combining an immunomodulator with a chemotherapy agent in chondrosarcoma-a proof of concept with mifamurtide. (PubMed, Med Oncol) - "These results highlight the importance of TAMs in modulating treatment response. This study provides a preclinical proof of concept for the efficacy of combining mifamurtide with doxorubicin in managing chondrosarcoma, highlighting the potential of immunomodulator and chemotherapy co-treatment in improving treatment outcomes."

Journal • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor • TLR4

Is There a Role for Mifamurtide in Nonmetastatic High-Grade Osteosarcoma? Results From the Italian Sarcoma Group (ISG/OS-2) and Spanish Sarcoma Group (GEIS-33) Trials. (PubMed, J Clin Oncol) - "In this merged analysis with a risk-adapted strategy for nonmetastatic osteosarcoma, the group with unfavorable prognoses, identified by Pgp expression, performed well when mifamurtide, combined with HDIFO in case of poor response, was administered after surgery."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • ABCB1

Aberrant Somatic Hypermutation Plays Minor Role in the Evolution of Molecular Alterations at Recurrence in PCNSL (AAN 2025) - "Samples analyzed using MSK-HemePACT panel...aSHM was observed in the archival tumor samples that were not shared with the CSF samples. Moreover, aSHM seemed to be a minor contributor to mutations identified in CSF samples. Possibly, aSHM does not play a role in PCNSL after initial diagnosis and therapy, accounting for sparsity of mutations caused by aSHM in recurrent/refractory CSF samples."

CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • ARSI