Researchers at Brigham and Women’s Hospital have moved one step closer to being able to predict a patient’s response to multiple prostate cancer therapies at one time. Their solution involves using an implantable and retrievable device about the size of a grain of rice. The device recently received Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA), and clinical trials are underway.
Oliver Jonas, PhD, who runs the Laboratory for Bio Micro-Devices in the Brigham’s Department of Radiology, invented the 820 µm implantable microdevice (IMD) to perform high-throughput, in vivo drug sensitivity testing in solid tumors. The device can deliver intratumal microdoses of drugs or combinations of drugs, allowing each therapy to interact with the tumor in its native microenvironment.
“The medical field has advanced to the point where we can use genomics and other markers to predict who will respond to a given therapy, but to date, only a small subset of patients is benefitting from this approach,” Dr. Jonas said. “The IMD represents a way to more quickly test therapy response in a localized, precise manner, and to do that for many different therapies at once. As a result, patients are spared the toxicity of systemic drug administration.”
A Look at the IMD Platform
The first fully implantable and retrievable device to deliver cancer therapies, the IMD platform contains 20 micro-reservoirs, each containing a unique drug or drug combination. The device is placed directly into a patient’s tumor percutaneously using a conventional thin interventional needle. It remains in situ for a predetermined duration of several hours to days. During this time, drugs from the micro-reservoirs are released into spatially separate and confined regions of the tumor in a time- and concentration-dependent manner.
Up to three days later, the IMD and surrounding tissue are retrieved from the patient’s tumor by minimally invasive biopsy or surgical means. The device/tissue specimen is then analyzed by a variety of methods to characterize drug response in the tissue.
“Because my research lab is located in the hospital, I’ve been able to work in close physical proximity to the surgical, interventional radiology and pathology teams that are an integral part of the process,” Dr. Jonas said.
Novel Translational and Regulatory Pathways
The IMD is a drug/device combo for which no clear precedents existed. As a result, Dr. Jonas paid special attention to the engineering design and testing process to integrate the novel technology into existing clinical workflows and reduce patient risk.
Manufacturing a combination drug/device is complicated, he noted. For example, while devices must undergo sterilization through irradiation or other methods, drugs cannot be irradiated without compromising their activity.
“We had to take both the drug and device sides into consideration to make sure the final product is sterile, has low endotoxin burden and is safe to use in patients,” he said.
Dr. Jonas also took a unique path through regulatory review with the FDA. The first hurdle was determining which FDA group—the Center for Drug Evaluation and Research (CDER) or the Center for Devices and Radiological Health—would have jurisdiction over the review process.
The FDA designated the IMD as a combination product that would fall under the IND category and be reviewed by the CDER. After multiple consultations among clinicians, engineers and regulators, along with iterations and evolution of the technology platform based on acquired clinical data and user feedback, Dr. Jonas received an IND for the device.
“We worked closely with the FDA and the Brigham’s Institutional Review Board to anticipate the measurements and safety features the FDA would require to ensure the device is manufactured to the highest-quality control standard and that we’re using the device in the safest way possible,” Dr. Jonas said.
The Future of Personalized Medicine
Adam S. Kibel, MD, chief of the Division of Urology, praised Dr. Jonas’ work and the ability of the Brigham to bring together innovative minds and clinical expertise to develop a complete understanding of the benefits of using multimodal therapy to treat patients with localized prostate cancer.
“Understanding which drug or combination of drugs is effective in a particular tumor in an individual patient is crucial to fully realizing the benefits of personalized medicine,” he said. “From a clinical perspective, innovations like the IMD will help us provide targeted care for patients, minimize their suffering and improve their quality of life.”