Mepact (mifamurtide) / Medison, Takeda - LARVOL DELTA

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

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

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

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

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

Developing a 3D bone model of osteosarcoma to investigate cancer mechanisms and evaluate treatments. (PubMed, FASEB J) - "Incubating bone cores with mifamurtide induced a reduction of cellular markers and an increase in bone volume. This 3D bone core model has the potential to investigate osteosarcoma tumor microenvironment and provides a representative model for evaluation of novel therapies."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD68 • ENG

SARCOMA DRUG APPROVALS IN LATIN AMERICA COMPARED TO THE FDA AND EMA: AN ANALYSIS BY THE LACOG SARCOMA GROUP (CTOS 2024) - "The FDA led the approvals, granting authorization to 18 of these treatments first, with Trabectedin being the sole exception, approved earlier by the EMA and COFEPRIS. Mifamurtide is the only new drug against sarcoma licensed by the EMA but not by the FDA... The observed discrepancies in drug approval timelines and the lower number of drug approvals in Latin American countries, as compared to those by the FDA and EMA, may exacerbate disparities in treatment accessibility for sarcoma patients in these regions. Approvals of sarcoma drugs by regulatory agencies of Latin American countries were more frequently conditioned to phase 3 trials and overall survival benefit."

Oncology • Sarcoma • Solid Tumor

Long-Circulating and Targeted Liposomes Co-loading Cisplatin and Mifamurtide: Formulation and Delivery in Osteosarcoma Cells. (PubMed, AAPS PharmSciTech) - "The constructed long-circulating targeted liposomes co-loading DDP and mifamurtide significantly inhibited the cell viability, migration, invasion and cell apoptosis of MG-63 cells, improving the antitumor effect of DDP and mifamurtide in vitro. The constructed liposomal delivery system is suitable for co-loading DDP and mifamurtide to achieve active tumor targeting, supplying a new strategy for the treatment of OS."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • MMP14

IS THERE A ROLE FOR MIFAMURTIDE IN NONMETASTATIC EXTREMITY HIGH-GRADE OSTEOSARCOMA PATIENTS? RESULTS OF PROSPECTIVE ITALIAN SARCOMA GROUP (ISG/OS-2) AND SPANISH SARCOMA GROUP (GEIS-33) TRIALS (CTOS 2024) - No abstract available

Clinical • Metastases • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

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

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

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

Cost-Effectiveness Analysis of Osteosarcoma Treatment: Insights From a Systemic Literature Review (ISPOR-EU 2024) - "The literature search identified only one intervention, mifamurtide, with economic evaluations in osteosarcoma and thus, indicating a significant unmet need. Mifamurtide in combination with chemotherapy was a cost-effective option compared to chemotherapy alone. Further research is essential to assess the economic impact of emerging therapies for this rare disease."

Cost effectiveness • HEOR • Review • Oncology • Osteosarcoma • Rare Diseases • Sarcoma • Solid Tumor

Chondrosarcoma Co-Culture 3D Model─An Insight to Evaluate Drugs Acting on TAMs. (PubMed, ACS Biomater Sci Eng) - "Finally, mifamurtide, an immunomodulator acting on TAMs, was evaluated on the most in vitro relevant model: 3D co-culture CH2879 model. Our results showed that it is now possible to develop 3D models that very accurately mimic what is found in vivo with the possibility of evaluating treatments specific to a tumor cell component."

Journal • Hematological Malignancies • Leukemia • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • MMP9 • PTGS2

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

Biomarker • Trial completion date • Trial primary completion date • Tumor microenvironment • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD68 • PD-L1

Sarcoma drug approvals in Latin America compared to the FDA and EMA: An analysis by the LACOG Sarcoma Group. (ASCO 2024) - "The FDA led the approvals, granting authorization to 18 of these treatments first, with Trabectedin being the sole exception, approved earlier by the EMA and COFEPRIS. Mifamurtide is the only new drug against sarcoma licensed by the EMA but not by the FDA... The observed discrepancies in drug approval timelines and the lower number of drug approvals in Latin American countries, as compared to those by the FDA and EMA, may exacerbate disparities in treatment accessibility for sarcoma patients in these regions. Approvals of sarcoma drugs by regulatory agencies of Latin American countries were more frequently conditioned to phase 3 trials and overall survival benefit."

Oncology • Sarcoma • Solid Tumor

Phase II study in pediatric and AYA patients with non-metastatic high-grade extremity osteosarcoma with a risk-adapted strategy based on P-glycoprotein (ISG/OS-2): A correlative study on tumour immune microenvironment. (ASCO 2024) - P, P2 | "Tumour immune microenvironment prognostic gene signatures have been identified for risk stratification of pts with osteosarcoma, regardless of treatment with mifamurtide. Importantly, we have developed a mifamurtide-specific signature that predicts EFS. This promising tool might be used to select pts who could benefit from adjuvant mifamurtide."

Clinical • Metastases • P2 data • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor

ISG/OS-2: ABCB1/P-glycoprotein Expression as Biologic Stratification Factor for Patients With Non Metastatic Osteosarcoma (clinicaltrials.gov) - P2 | N=225 | Completed | Sponsor: Italian Sarcoma Group | Active, not recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ Apr 2024 | Trial primary completion date: Dec 2023 ➔ Apr 2024

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

Micros: Tumor Microenvironment in Patients With Localized Osteosarcoma Treated With Mifamurtide: a Translational Study (clinicaltrials.gov) - P=N/A | N=80 | Recruiting | Sponsor: Istituto Ortopedico Rizzoli | Trial primary completion date: Dec 2023 ➔ Jun 2024

Biomarker • Trial primary completion date • Tumor microenvironment • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD68 • PD-L1

Tumor-associated macrophages: A tool for the treatment of chondrosarcoma (Sarcoma-RC 2024) - "In addition, the cocultured tumoroid showed chemoresistance to doxorubicin with IC50 two times higher compared to the monoculture model. Taken together, these results point to the development of a relevant preclinical model mimicking cell/matrix and cell/cell interactions that can be used to evaluate new treatments, with the aim of improving the management of this orphan pathology."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor • MMP9

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

Enrollment closed • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

ICONIC (IMPROVING OUTCOMES THROUGH COLLABORATION IN OSTEOSARCOMA): A PROSPECTIVE OBSERVATIONAL COHORT STUDY FOR NEWLY DIAGNOSED OSTEOSARCOMA PATIENTS IN THE UNITED KINGDOM (UK) (CTOS 2023) - P=N/A | "Multi-agent adjuvant chemotherapy treatment has been initiated in 133 patients, 99 (74%) of which included methotrexate and 50/78 (64%) of patients eligible to receive adjuvant mifamurtide following NICE recommendations have received at least 1 dose (median 27, range 1-49). ICONIC is the first prospective observational cohort study to recruit UK patients of all ages with newly diagnosed OS. Initial analyses have demonstrated the feasibility of comprehensive data and sample collection and identified differences in systemic management of patients across the country worthy of further investigation ICONIC provides a unique resource that will allow for better understanding of the biology of OS and aid development of new biomarkers and novel therapeutic approaches. Analyses are aligned with objectives within the newly formed European consortium, Fight Osteosarcoma Through European Research (FOSTER) where possible and provide opportunities for wider collaboration."

Clinical • Observational data • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Blockade of IL-10 Signaling Ensures Mifamurtide Efficacy in Metastatic Osteosarcoma. (PubMed, Cancers (Basel)) - "We provide experimental evidence that the synergic use of an anti-IL-10 antibody in combination with mifamurtide causes a significantly increased mortality rate in highest-grade OS cells and lower metastasis in an in vivo model compared with mifamurtide alone. Overall, our data suggest that mifamurtide in combination with an anti-IL-10 antibody could be proposed as a new treatment protocol to be studied to improve the outcomes of OS patients."

Journal • Metastases • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • IL10