EUS-FNB samples will be used for organoid cultures, which will be co-cultured with cancer associated fibroblasts derived from the surrounding stroma of the lesion. The organoid cultures will be used for pharmacotyping using relevant chemotherapeutic agents used in the clinic, and the organoid's response compared with the patient's response.

Aim: To use organoids cultured from diagnostic endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) samples from patients with pancreatic ductal adenocarcinoma (PDAC) for pharmacotyping.

Patients will be included at Herlev Hospital. EUS-FNB will be performed using a standard 19 or 22-gauge FNB needle. Oncological treatment administration and evaluation of treatment response will be performed by physicians at the Department of Oncology, Herlev Hospital as per current standard of care. Following EUS-FNB procedure, the tissue is immediately transferred to basal medium and epithelial cells as well as CAFs released by digestion and epithelial cells cultured in Matrigel. Following expansion of the organoids and prior to pharmacotyping, next generation sequencing (NGS) analysis will be performed on both the baseline and the organoid sections to validate if the outgrown organoids correspond to the cancer cells from the baseline sample.

Organoid co-cultures are exposed to six to ten different drug concentrations ranging from 10-12-10-4 M (depending on the individual drug properties). Systemic agents and combinations used in the standard clinical practise will be used. Computed tomography (CT) scan of the thorax and abdomen are performed at baseline (within 28 days prior to first study drug administration) to assess efficacy of the drugs in patients.

Inclusion Criteria:

• Signed informed consent
• Histopathological confirmation of PDAC and planned standard first-line treatment prior to entering this study OR Patients suspected of primary locally advanced, non-metastatic PDAC based on cross-sectional imaging undergoing diagnostic standard of care (SOC) EUS-FNB procedure
• Age > 18 years and older
• Life expectancy greater than 3 months
• ECOG/WHO Performance Status (PS) 0-1
• Patients must have normal organ and marrow function as defined below:
• White blood cell count (WBC) ≥ 3 x 10⁹/L
• Platelet count ≥ 100 x 10⁹/L
• Serum bilirubin ≤1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin ≤ 50 mmol/L)
• PP ≥ 40 or INR ≤ 1.5
• Serum creatinine ≤ 1.5 x ULN or CrCl ≥ 40 mL/min (using the Cockcroft-Gault formula)

Exclusion Criteria:

• Contraindications for nurse administered propofol sedation (NAPS)
• Contraindications for EUS-FNB procedure

Patients with histopathological confirmation of pancreatic ductal adenocarcimona, ineligible for surgery, planned to start standard first line treatment