Personalized Cell Therapy.

Patient Scheduler: A ‘Patient Scheduler’ acted as central point of contact between Bionical Emas, sites, and the manufacturing lab, dedicated to managing each patient’s schedule on the study. The Patient Scheduler maintained a master calendar of patient screening and treatment schedules, collaborated with the manufacturing lab prior to commencement of screening to assign the patient a date for producing their personalized vaccine, and reviewed screening assessment windows for patients who needed additional rounds of leukapheresis to produce sufficient vaccine. Due to the limited number of weekly slots available to manufacture the patient specific vaccine, the role of the Patient Scheduler was imperative to ensure study subject progressed on the study successfully.

Imaging Vendor: The study treatment was injected directly into the tumor, causing a local inflammatory response, resulting in an initial swelling of the tumor before subsequent shrinking due to necrosis. RECIST identifies disease progression as an increase in tumor size which would potentially have resulted in patients being prematurely discontinued from the study before tumor necrosis could be achieved. Therefore, Immune Related Response Criteria (irRC) was also implemented for tumor response measurements. We created an additional radiological endpoint and engaged a specialist central imaging vendor to highlight the tumor composition following treatment, and identify the parts of the tumor that were necrosis vs. live tumor.

Tumor Read & Recording: A 3-level location tiering system was created based on SDTM LOC lists to facilitate identification and tracking of tumors. This was required due to the specialist imaging and irRC criteria for tracking disease, and because the protocol allowed multiple target tumors per organ to be injected. This linked data gathered from lesion measurements, injection sites and biopsies, and provided the Sponsor with a high level of granularity in location identification.

Medical Monitor Engagement: To ensure that patients were not discontinued prematurely due to increased tumor size as a result of initial immune response, constant communication and reeducation of the sites regarding tumor response evaluations was required. Our Medical Monitors discussed individual patients with the Investigators and encouraged them to keep the patient on the trial if they were considered to still be in the treatment’s immune response stage. Our clinical operations team proactively followed up with the site prior to each biopsy timepoint to remind them of the need for these discussions.

Specialist Lab Vendor: SWe identified and managed multiple lab vendors to assess specialist tumor markers such as circulating DNA, to support physicians and patients in making their decision to stay on treatment when investigator tumor response evaluations suggested initial disease progression.

Specialist Site Staff: Robust feasibility was undertaken to ensure that the study sites that were selected had an interventional radiologist available to conduct ultrasound- or CT-guided intratumoral injections and concurrently take multiple biopsies. They also needed to be flexible to allow scheduling of procedures to fit in with other study scheduling for the patient. We worked in collaboration with the client to develop a training video to show the successful application and technique of intratumoral injection of the study treatment.

Site Budgets: Specialized processes and assessments required for cell therapy studies that are often not part of a site’s normal practice which, unless managed closely and transparently, early-on with both the site and the sponsor, can result in very high site costs. Close management of the investigator site fees and fair market value benchmarking from the outset meant that we were able to avoid unforeseen site costs.

Close Client Partnership: Given the complexity of the study, it was paramount that our project team became an extension of the Sponsor team. Our strong, transparent and open relationship allowed us to support our client in early consideration of the manufacture up-scaling process, which is important to ensure a cost effective process, and to recommend a move from a Sponsor selected eDC that was not appropriate for the complexity of the study to a successful system.