Development and optimization of highly effective treatments in patients with head and neck cancer using in situ implantable microdevices

Brigham And Women'S Hospital, Boston MA

Investigators

Abstract

The ability to predict the optimal therapy for an individual patient is a major unmet need in the treatment of cancer and other diseases. The majority of therapies in clinical cancer treatment, particularly cytotoxics and immunotherapies as well as combinations of multiple drugs, have no reliable predictor of response. This uninformed therapy selection is highly inefficient and likely leads to reduced therapeutic success rates, increased side effects and excessive economic expenditures. We have developed a “lab-in-a-patient” implantable microdevices (IMD) which release spatially discrete microdoses of up to 20 different drugs into locally confined regions of the patient’s tumor, and measures the response to each localized treatment using a range of histological, immunological, transcriptomic and other tumor-drug response markers. Each drug-tumor readout measures drug efficacy in a concentration- dependent manner, and identifies predictive biomarkers of response and resistance directly within each treatment zone. Our group has developed the IMD technology from ideation through prototyping, animal testing and into early clinical testing, where the IMD has been tested for safety and feasibility in eight cancer types and across multiple institutions. We have shown in two landmark publications that IMD readouts may be capable of predicting responses to chemotherapy in glioblastoma patients, and that IMD readouts are capable of predicting immunotherapy responses in breast cancer models and can be used to efficiently screen for novel and highly effective therapies. This project proposes an academic-industrial collaboration which builds on the technical and early clinical advances made to date, in order to transition the IMD technology from a demonstration of possibility to a status useful for therapy selection and patient stratification in the clinical oncology and drug development setting. We will conduct a clinical study in head and neck squamous cell carcinoma (HNSCC) patients that serves to validate the performance of the IMD in a statistically significant cohort to effectively predict patients’ clinical response to first and second line immunotherapy and chemotherapy. This data will be pivotal towards regulatory approvals and broader clinical uptake of the technology which will be led by our commercial partner Kibur Medical. Secondly, we will use several reservoirs of the IMD to test key in situ pharmacodynamic properties of a novel antibody cytokine conjugate (provided by our industry collaborator Scare, Inc.) directly in patients with HNSCC, in order to dramatically expedite the development of this potentially game-changing treatment class. This aim validates a key aspect of successful IMD commercialization, namely the ability to serve as a platform for early in vivo testing of novel drug candidates, and will serve as a blueprint for uptake by other drug developers. Thirdly, we will enable clinical use of the IMD in harder- to-reach lesions in order to make the platform suitable for end users across a broad range of cancer types. Taken together, the proposed project spans technical, translational and regulatory development that support broad clinical deployment and commercialization of the IMD technology.