An Implantable Microdevice in Soft Tissue Sarcoma
| Therapeutic development in soft tissue sarcoma is limited by the rarity and heterogeneity of the disease and is an increasingly cost-prohibitive undertaking in both academic and industry settings. The community can benefit from methods to generate clinical data on current and novel therapeutic agents prior to initiation of first-in-human trials. These data can be used to inform clinical decisions for currently available treatment options and serve as motivation to proceed with dedicated clinical trials of investigational drugs. One method to accelerate data generation in sarcoma drug development is a drug-eluting implantable microdevice. We have developed device roughly the size of a grain of rice which can expose a single tumor to multiple potential therapies within a single patient. The device has been deployed in multiple settings including mouse models of human tumors and in patients with brain tumors at the Mass General Brigham Cancer Institute. It can be safely implanted and removed in each setting, and the surrounding tissue can be analyzed for markers of drug response. In each setting, in situ drug response has correlated with systemic response to that same treatment. We aim to utilize our tumor microdevice in patients with soft tissue sarcoma who are likely to require systemic therapy. The goals of this proposal are to demonstrate that our microdevice device can be safely placed and removed in patients with treatment-naïve sarcomas, and to analyze the effect of multiple drugs on an individual tumor. Readouts will include markers of cell death, DNA damage, proliferation, and changes to the immune component of the tumor (tumor microenvironment). For therapies indented to target a specific pathway, we will include assays aimed at investigating the unique effect of that drug such as expression profiling or single cell assays. A single device can be loaded with up to 20 drugs or combinations of drugs including chemotherapy, immunotherapy, and investigational agents. Systemic exposure to microdevice agents is less than 1/100,000 of typical drug dosing, which allows for testing of drugs and combinations which have not been tested in patients before without risking toxicity. A successful study will not only demonstrate that this method is feasible in soft tissue sarcoma but generate data that is useful to patients. For approved therapies, data from microdevices can be used to inform treatment options. This will allow providers to pick the most active agent for an individual tumor. For novel therapies, data can be aggregated across all participants to identify new vulnerabilities. We anticipate the data generated from this study will serve as motivation for dedicated clinical trials of novel agents in patients with soft tissue sarcoma. |