Early Feasibility Clinical Investigation to Assess YntraDose™ as a Neoadjuvant Treatment for LA-PDAC

Early Feasibility Clinical Investigation Using a Novel 90-Yttrium-based Internal Radiotherapy Platform, YntraDose™ in Unresectable Locally Advanced Pancreatic Adenocarcinoma (LA-PDAC) as an add-on Therapy to First-line SOC (Chemotherapy)

The goal of this clinical investigation is to learn if a new type of radiotherapy works to treat pancreatic cancer that cannot be removed surgically. It will also learn about the safety of the new treatment when combined with chemotherapy. The treatment involves injecting a radioactive implant (medical device) directly into the pancreatic tumour on one occasion only. The main questions it aims to answer are:

• Is the new treatment safe and tolerable when used in combination with standard of care chemotherapy.
• Is it feasible to inject the new treatment directly into a patient's pancreatic tumour.
• What is the impact of this new treatment on a patient's quality of life including a pain evaluation.
• To assess how the pancreatic tumour responds to the treatment during the 3 month follow up.

Participants will:

• Participate in the research study for approximately 7 months and will receive standard of care chemotherapy throughout their participation.
• Participants will initially receive standard of care chemotherapy which will be stopped after 2 months to reassess the tumor by a multidisciplinary tumor board. Chemotherapy will resume and the test device will be administered between chemotherapy treatments. The new treatment involves a single injection of the radioactive implant directly into the pancreatic tumour. Following treatment, the participant's standard of care chemotherapy will resume.
• Participants will attend follow up visits over 3 months.
• Participants will visit the clinic on 8 separate occasions and on one occasions, will remain in hospital for 2 nights/3 days to receive treatment with the new radiotherapy device and to monitor for safety.
• Participants will complete questionnaires to check how the treatment is affecting their daily lives and pain levels.
• Participants will undergo different types of imaging (scans) such as CT, MRI.
• Participants will have bloods and urine taken to monitor safety.

The study is a multicentre, open-label, prospective, early feasibility clinical investigation to assess the safety, tolerability and feasibility of YntraDose™ treatment following percutaneous administration under Ultrasound/CT guidance.

The investigational device is YntraDose™, which is a locoregional therapy device used for percutaneous radio-ablation of solid tumours delivering targeted radiation using Y-90 microspheres injected directly into the tumour site, within a glue matrix holding the Y-90 microspheres in place. The product is designed for single use.

YntraDose™ is indicated as a neoadjuvant therapy and add-on treatment to first-line standard of care therapy in patients with unresectable LA-PDAC. The aim of YntraDose™ development is to combine it with chemotherapy standard of care (FOLFIRINOX or gemcitabine/nab-paclitaxel). Combining systemic chemotherapy with radiotherapy for local disease control, may improve time to progression of local disease, pain control, performance status, and quality of survival, and in a neoadjuvant setting may convert tumours to resectability.

YntraDose™ will be administered intratumorally and percutaneously into the pancreas under ultrasound/CT guidance. The Y-90 microspheres have been designed to deliver a localized distribution of beta radiation within the target tumour. The radiation from these particles causes direct damage to cancer cell DNA, which renders them incapable of further cell division and proliferation, leading to tumour shrinkage. The glue matrix is a hydrogel that polymerizes in the site of implantation and serves to retain the Y 90 radioactive microspheres in-situ facilitating the effect of radioactive microspheres in the tumoural tissue only.

Ten (10) patients with unresectable locally advanced pancreatic ductal adenocarcinoma meeting the eligibility criteria will be recruited into the clinical investigation.

Inclusion Criteria (Main):

• Histologically or cytologically proven Pancreatic Adenocarcinoma.
• Stage of disease defined as unresectable Locally Advanced Pancreatic Cancer.
• No prior radiotherapy for pancreatic cancer.
• Target tumour with a minimum diameter of 2.6 cm and a volume of from 9 to 34 ml.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patient has acceptable hematological parameters including white and red blood counts, liver and renal function that makes them suitable to receive SoC chemotherapy as per local clinical practice.
• Life expectancy of ≥6 months at screening.

Exclusion Criteria (Main):

• Evidence of distant metastases based on the restaging process after two months of induction chemotherapy identified using CT/MRI/18 FDG PET assessment.
• Evidence of switch from unresectable status to resectable status of disease after two months of induction chemotherapy.
• More than one primary lesion, if one of the primary lesions is not a good candidate for debulking with YntraDose™, due to clinical reasons and/or decision made by the local MDTB.
• ECOG is higher than 1.
• History of malignancy in the last 3 years.
• Blood clotting disorders (INR > 1.5, PLT < 50,000/µl - risk of bleeding during organ puncture).
• Active systemic or local infection (e.g. peritonitis, abscess).
• Severe organ failure (e.g. end-stage liver, kidney, heart failure).
• Cardiological and other diseases that threaten the use of anesthesia.
• Pancreatitis (acute or exacerbation of chronic inflammation).