Clinical trials in sarcoma
PERELI
The PERELI trial was recently approved by Incyte to test pemigatinib in dedifferentiated liposarcomas in Scandinavia (PIs: Helena Nyström from the Division of Oncology, Department of Clinical Sciences, Lund, Lund University and Kjetil Boye from the Department of Oncology, Oslo University Hospital, Oslo, Norway. Liposarcomas overexpress FGF receptor substrate 2 (FRS2), which are believed to render these cells susceptible to FGFR kinase inhibitors1,2
We are lab partners in this clinical trial and will analyse pateint material, as well as furhter investigate why FRS2 amplification leads to sensitivty to FGFR inhibitors.
1 Hanes, R. et al. Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma. Cells 8, doi:10.3390/cells8020189 (2019).
2 Zhang, K. et al. Amplification of FRS2 and activation of FGFR/FRS2 signaling pathway in high-grade liposarcoma. Cancer Res 73, 1298-1307, doi:10.1158/0008-5472.CAN-12-2086 (2013).
Biomarkers for response to Pembrolizumab in sarcoma (NoSarC PD1)
Immune therapy has been shown to be promising in several other cancer types, such as melanoma, renal cell and non-small cell lung cancer. Within the last four years, the FDA (U.S. Food and Drug Administration) has approved three immune checkpoint inhibitors as treatment for
melanoma, and approval to treat several other cancer types are expected in the coming years.
Based on the success in other cancers, a number of immunotherapy-based clinical trials are being implemented for sarcomas. Among these are therapies against the checkpoint inhibitor PD-1. It has been suggested that tumours with high mutational load may respond better to treatment with this checkpoint inhibitor than tumours with less mutational load. Due to the high level of genomic rearrangements and fusion genes seen in sarcoma, this cancer type is believed to be particularly amenable for immunotherapy. However, despite the success of immunotherapies, only a fraction of the patients experience objective tumour response to checkpoint inhibitors. Identifying and validating better biomarkers for such immunotherapies are essential for personalized cancer immunotherapy, and stratification of patients that will most likely benefit is strongly needed.
This study is an extension of the Merck sponsored phase II open-label multicenter trial, SARC 028 (PI: Hussein Tawbi), utilizing the anti-PD-1 antibody, pembrolizumab, as single agent therapy in sarcoma patients with refractory metastatic or locally advanced disease. The accrural was completed in 2015. The samples from the SARC 028 trial are characterised to identify novel predictive biomarkers for anti-PD-1 treatment response in sarcomas.