TY - JOUR
T1 - Outcomes from a mechanistic biomarker multi-arm and randomised study of liposomal MTP-PE (Mifamurtide) in metastatic and/or recurrent osteosarcoma (EuroSarc-Memos trial)
AU - Barnes, David J
AU - Dutton, Peter
AU - Bruland, Øyvind
AU - Gelderblom, Hans
AU - Faleti, Ade
AU - Bühnemann, Claudia
AU - van Maldegem, Annemiek
AU - Johnson, Hannah
AU - Poulton, Lisa
AU - Love, Sharon
AU - Tiemeier, Gesa
AU - van Beelen, Els
AU - Herbschleb, Karin
AU - Haddon, Caroline
AU - Billingham, Lucinda
AU - Bradley, Kevin
AU - Ferrari, Stefano
AU - Palmerini, Emanuela
AU - Picci, Piero
AU - Dirksen, Uta
AU - Strauss, Sandra J
AU - Hogendoorn, Pancras C W
AU - Buddingh, Emmeline
AU - Blay, Jean-Yves
AU - Cleton-Jansen, Anne Marie
AU - Hassan, Andrew Bassim
N1 - © 2022. The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Acetylmuramyl-Alanyl-Isoglutamine/analogs & derivatives
KW - Bayes Theorem
KW - Biomarkers
KW - Bone Neoplasms/pathology
KW - Humans
KW - Liposomes
KW - Neoplasm Recurrence, Local/drug therapy
KW - Osteosarcoma/pathology
KW - Phosphatidylethanolamines
KW - Osteosarcoma
KW - Muramyl tripeptide
KW - Phase II trial
KW - Bayesian
KW - Sarcoma
KW - Bone neoplasm
KW - Rare cancer
U2 - 10.1186/s12885-022-09697-9
DO - 10.1186/s12885-022-09697-9
M3 - Article
C2 - 35672690
SN - 1471-2407
VL - 22
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 629
ER -