Pasireotide as maintenance treatment in SSTR2/3/5-expressing synovial sarcoma and desmoplastic small round cell tumor: The PAMSARC study

BackgroundDesmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and adults with male predominance. It originates from the serosal surface of the abdominal cavity and the hallmark characteristic of DSRCT is the EWSR1::WT1 gene fusion. Synovial sarcoma (SySa) is also a rare fusion-gene driven (SS18::SSX1, SS18::SSX2, or rarely, SS18::SSX4) soft-tissue sarcoma that frequently affects adolescents and adults. Current management of DSRCT and SySa includes chemotherapy, radiation and aggressive cytoreductive surgery. Despite advances in multimodal therapy, outcomes remain poor with frequent disease recurrence and very limited options for patients with advanced disease. Selected somatostatin receptor (SSTR) family members, i.e., SSTR2, SSTR3 and SSTR5, are frequently overexpressed in DSRCT and SySa, providing the rationale for treatment with somatostatin analogues (SSA). Pasireotide is a SSA with high affinity for SSTR1, -2, -3, and -5 and is approved for the treatment of Cushing’s disease and acromegaly and has also shown activity in other cancers. In patients with advanced stage DSRCT and SySa, conventional chemotherapeutic approaches frequently lead to disease response, however, the duration of progression-free time after chemotherapy is short. The targeted approach with pasireotide after initial intensive chemotherapy may have the potential to significantly improve outcome.Trial designThe primary aim of the study is to assess the clinical efficacy of pasireotide maintenance therapy for prolonging progression-free (PFS) and overall survival (OS) in patients with advanced SySa and DSRCT with expression of SSTR2/-3/-5, as determined via transcriptome sequencing. Pasireotide is applied in adults with 60 mg and in adolescents dose adjusted via intragluteal depot injection every 28±3 days. The sample size is planned for the entire study population, sensitivity analysis in adolescents and adults are included. The sample size is calculated assuming exponential data, planning for a power of 90% to detect a hazard ratio of 0.5. With a sample size of n=28, the expected number of events during the study is 22.Clinical trial identificationEU Clinical Trial (CT) 2024-511935-86-00-00.Legal entity responsible for the studyHeidelberg University Hospital.FundingRecordati.DisclosureR.F. Schlenk: Financial Interests, Institutional, Research Funding: AstraZeneca, Boehringer Ingelheim, Pfizer, PharmaMar, Roche, Recordati; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo, Pfizer, AstraZeneca; Financial Interests, Personal, Advisory Board: Abbvie, Daiichi Sankyo, Jazz, Pfizer. C. Heining: Financial Interests, Institutional, Research Funding: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim. M. Sparber Sauer: Financial Interests, Personal, Advisory Board: Roche, Sobi; Financial Interests, Institutional, Research Funding: Bayer. A. Floercken: Financial Interests, Personal, Other, Honoria: Boehringer Ingelheim; Financial Interests, Personal, Officer, Honoraria: PharmaMar. C. Deinzer: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: PharmaMar; Financial Interests, Personal, Other, Travel Grant: Boehringer Ingelheim, Deciphera, Pierre Fabre. V. Gaidzik: Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals, Abbvie, Boehringer-Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Janssen, Abbvie; Financial Interests, Personal, Other, Travel Grant: Abbvie. C.M. van Tilburg: Financial Interests, Personal, Advisory Board: Alexion, Bayer, Novartis. S. Fröhling: Financial Interests, Personal, Advisory Board: Bayer, Illumina, Roche; Financial Interests, Personal, Invited Speaker: Amgen, Eli Lilly, Illumina, PharmaMar, Roche. All other authors have declared no conflicts of interest.