Outcomes from a mechanistic biomarker multi-arm and randomised study of liposomal MTP-PE (Mifamurtide) in metastatic and/or recurrent osteosarcoma (EuroSarc-Memos trial)

BMC Cancer. 2022 Jun 8;22(1):629. doi: 10.1186/s12885-022-09697-9.


The phase III clinical study of adjuvant liposomal muramyl tripeptide (MTP-PE) in resected high-grade osteosarcoma (OS) documented positive results that have been translated into regulatory approval, supporting initial promise for innate immune therapies in OS. There remains, however, no new approved treatment such as MTP-PE for either metastatic or recurrent OS. Whilst the addition of different agents, including liposomal MTP-PE, to surgery for metastatic or recurrent high-grade osteosarcoma has tried to improve response rates, a mechanistic hiatus exists in terms of a detailed understanding the therapeutic strategies required in advanced disease. Here we report a Bayesian designed multi-arm, multi-centre, open-label phase II study with randomisation in patients with metastatic and/or recurrent OS, designed to investigate how patients with OS might respond to liposomal MTP-PE, either given alone or in combination with ifosfamide. Despite the trial closing because of poor recruitment within the allocated funding period, with no objective responses in eight patients, we report the design and feasibility outcomes for patients registered into the trial. We demonstrate the feasibility of the Bayesian design, European collaboration, tissue collection with genomic analysis and serum cytokine characterisation. Further mechanistic investigation of liposomal MTP-PE alone and in combination with other agents remains warranted in metastatic OS.

Keywords: Bayesian; Bone neoplasm; Muramyl tripeptide; Osteosarcoma; Phase II trial; Rare cancer; Sarcoma.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives
  • Bayes Theorem
  • Biomarkers
  • Bone Neoplasms* / pathology
  • Humans
  • Liposomes
  • Neoplasm Recurrence, Local / drug therapy
  • Osteosarcoma* / pathology
  • Phosphatidylethanolamines


  • Biomarkers
  • Liposomes
  • Phosphatidylethanolamines
  • mifamurtide
  • Acetylmuramyl-Alanyl-Isoglutamine